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Anaïs Bailles#, Giulia Serafini, Heino Andreas, Christoph Zechner, Carl D. Modes, Pavel Tomancak#
Anisotropic stretch biases the self-organization of actin fibers in multicellular Hydra aggregates.
Proc Natl Acad Sci U.S.A., 122(32) Art. No. e2423437122 (2025)
Open Access PubMed Source   

During development, groups of cells generate shape by coordinating their mechanical properties through an interplay of self-organization and prepatterning. Hydra displays a striking planar pattern of actin fibers at the organism scale, and mechanics influence the morphogenesis of biological structures during its prepatterned regeneration. However, how mechanics participate in the formation of an ordered pattern from a totally disordered state remains unknown. To study this, we used cellular aggregates formed from dissociated Hydra cells, which initially lose all actin polarity yet regenerate a long-range actin pattern. We showed quantitatively that the actin meshwork evolves from a disordered symmetric state to an ordered state in which rotational symmetry is broken, and translation symmetry is partially broken, with the nematic and smectic order parameters increasing over days. During the first hours, the actin meshwork displayed spatial heterogeneity in the nematic order parameter, and ordered domains separated by line defects progressively grew and fused. This suggests that local cell-cell interactions drive the transition from disorder to order. To understand the mechanism of ordering, we perturbed the tissue's physical constraints. We showed that while topology and geometry do not have a direct effect, anisotropic stretch biases the emerging orientation of the actin meshwork within hours. Surprisingly, although a Wnt head organizer is expected to play a role in the actin ordering, the stretch-associated alignment happened without the prior formation of a head organizer. This demonstrates the role of tissue mechanics in the alignment of the actin fibers during the disorder-to-order transition.
@article{Bailles9036,
author={Anaïs Bailles, Giulia Serafini, Heino Andreas, Christoph Zechner, Carl D. Modes, Pavel Tomancak},
title={Anisotropic stretch biases the self-organization of actin fibers in multicellular Hydra aggregates.},
journal ={Proceedings of the National Academy of Sciences of the United States of America},
volume={122},
issue ={32},
pages={null--null},
year=2025
}

Woorin Kim#, Nicola Schmidt, Matthias Jost, Elijah Mbandi Mkala, Sylke Winkler, Guangwan Hu, Tony Heitkam#, Stefan Wanke#
Diverging repeatomes in holoparasitic Hydnoraceae uncover a playground of genome evolution.
New Phytol, 247(3) 1520-1537 (2025)
Open Access PubMed Source   

The transition from an autotrophic to a heterotrophic lifestyle is associated with numerous genomic changes. These often involve large genomic alterations, potentially driven by repetitive DNAs. Despite their recognized role in shaping plant genomes, the contribution of repetitive DNAs to parasitic plant genome evolution remains largely unexplored. This study presents the first analysis of repetitive DNAs in Hydnoraceae genomes, a plant family whose members are holoparasitic. Repetitive DNAs were identified and annotated de novo. Abundant transposable elements and 35S ribosomal DNA in the Hydnora visseri genome were reconstructed in silico. Their patterns of abundance and presence-absence were individually and comparatively analyzed. Both Hydnoraceae genera, Hydnora and Prosopanche, exhibit distinct repeatome profiles which challenge our current understanding of repeatome and rDNA evolution. The Hydnora genomes are dominated by long terminal repeat retrotransposons, while the Prosopanche genomes vary greatly in their repeat composition: Prosopanche bonacinae with a highly abundant single DNA transposon and Prosopanche panguanensis with over 15% 5S rDNA, compared to ≤ 0.1% in the Hydnora genomes. The repeat profiles align with the phylogeny, geographical distribution, and host shifts of the Hydnoraceae, indicating a potential role of repetitive DNAs in shaping Hydnoraceae genomes to adapt to the parasitic lifestyle.
@article{Kim9014,
author={Woorin Kim, Nicola Schmidt, Matthias Jost, Elijah Mbandi Mkala, Sylke Winkler, Guangwan Hu, Tony Heitkam, Stefan Wanke},
title={Diverging repeatomes in holoparasitic Hydnoraceae uncover a playground of genome evolution.},
journal ={The New phytologist},
volume={247},
issue ={3},
pages={1520--1537},
year=2025
}

Anna Hadarovich, David Kuster, Maria Luisa Romero Romero, Agnes Toth-Petroczy
On the Evolution of Biomolecular Condensates: From Prebiotic Origins to Subcellular Diversity.
Annu Rev Cell Dev Biol, Art. No. doi: 10.1146/annurev-cellbio-101123-051723 (2025)
PubMed Source   

Biomolecular condensates provide a way to compartmentalize subcellular components with high temporal and spatial resolution, enabling rapid responses to signals and environmental changes. While the formation, components, and function of some condensates are well-characterized, their presence across organisms, their evolutionary history, and their origin are less well-understood. Here, we review the diversity of condensate components and highlight that not only disordered but also fully structured proteins are capable of driving condensate formation. We compare how proteomes of condensates overlap within and across species, and we present functionally analogous condensates across organisms. Additionally, we discuss the potential role of condensation in early life, suggesting that phase separation could have facilitated the selection and concentration of prebiotic molecules, promoting essential biochemical processes. We conclude that condensate-related organization principles are ubiquitously used across organisms from bacteria to mammals, and they potentially played a key role in prebiotic evolution, serving as primitive compartments for early biochemical processes.
@article{Hadarovich9033,
author={Anna Hadarovich, David Kuster, Maria Luisa Romero Romero, Agnes Toth-Petroczy},
title={On the Evolution of Biomolecular Condensates: From Prebiotic Origins to Subcellular Diversity.},
journal ={Annual review of cell and developmental biology},
volume={},
pages={1--1},
year=2025
}

Xiao Yan, David Kuster, Priyesh Mohanty, Jik Nijssen, Karina Pombo-García, Jorge Garcia Morato, Azamat Rizuan, Titus Franzmann, Aleksandra Sergeeva, Anh M Ly, Feilin Liu, Patricia M Passos, Leah George, Szu-Huan Wang, Jayakrishna Shenoy, Helen L Danielson, Busra Ozguney, Alf Honigmann, Yuna M Ayala, Nicolas L Fawzi, Dennis W Dickson, Wilfried Rossoll, Jeetain Mittal#, Simon Alberti#, Anthony Hyman#
Intra-condensate demixing of TDP-43 inside stress granules generates pathological aggregates.
Cell, 188(15) 4123-4140 (2025)
Open Access PubMed Source   

Cytosolic aggregation of the nuclear protein TAR DNA-binding protein 43 (TDP-43) is associated with many neurodegenerative diseases, but the triggers for TDP-43 aggregation are still debated. Here, we demonstrate that TDP-43 aggregation requires a double event. One is up-concentration in stress granules beyond a threshold, and the other is oxidative stress. These two events collectively induce intra-condensate demixing, giving rise to a dynamic TDP-43-enriched phase within stress granules, which subsequently transition into pathological aggregates. Intra-condensate demixing of TDP-43 is observed in iPS-motor neurons, a disease mouse model, and patient samples. Mechanistically, intra-condensate demixing is triggered by local unfolding of the RRM1 domain for intermolecular disulfide bond formation and by increased hydrophobic patch interactions in the C-terminal domain. By engineering TDP-43 variants resistant to intra-condensate demixing, we successfully eliminate pathological TDP-43 aggregates in cells. We suggest that up-concentration inside condensates followed by intra-condensate demixing could be a general pathway for protein aggregation.
@article{Yan9005,
author={Xiao Yan, David Kuster, Priyesh Mohanty, Jik Nijssen, Karina Pombo-García, Jorge Garcia Morato, Azamat Rizuan, Titus Franzmann, Aleksandra Sergeeva, Anh M Ly, Feilin Liu, Patricia M Passos, Leah George, Szu-Huan Wang, Jayakrishna Shenoy, Helen L Danielson, Busra Ozguney, Alf Honigmann, Yuna M Ayala, Nicolas L Fawzi, Dennis W Dickson, Wilfried Rossoll, Jeetain Mittal, Simon Alberti, Anthony Hyman},
title={Intra-condensate demixing of TDP-43 inside stress granules generates pathological aggregates.},
journal ={Cell},
volume={188},
issue ={15},
pages={4123--4140},
year=2025
}

Rudrarup Bose, Daniele Rossetto, Anju Tomar, Sanguen Lee, Sheref S Mansy, T-Y Dora Tang
Protometabolically Generated NADH Mediates Material Properties of Aqueous Dispersions to Coacervate Microdroplets.
Biomacromolecules, Art. No. doi: 10.1021/acs.biomac.5c00349 (2025)
Open Access PubMed Source   

Macromolecular assembly between biomolecules dictates the material state of chemically complex aqueous dispersions such as the cytoplasm. The formation of protein precipitates, fibers, or liquid droplets have been associated with metabolic regulation and disease. However, the effect of metabolic flux on the material properties of aqueous dispersions remains underexplored. Here, we use the protometabolic reduction of NAD+ to NADH by pyruvate to study the effect of NADH production on the phase separation properties of polyarginine. We show that reduction of NAD+ in the presence of polyarginine can tune the material properties of the dispersion between precipitates, homogeneous solution, and liquid droplets depending on the buffer concentration. In situ droplet formation results in 2-3 times higher reaction rate and NADH yield, compared to homogeneous solution. Our study provides a setting for coupling protometabolism to active protocell environments in the absence of enzymes and sheds light on the self-regulation of metabolic flux on mediating biomolecular phase separation.
@article{Bose9025,
author={Rudrarup Bose, Daniele Rossetto, Anju Tomar, Sanguen Lee, Sheref S Mansy, T-Y Dora Tang},
title={Protometabolically Generated NADH Mediates Material Properties of Aqueous Dispersions to Coacervate Microdroplets.},
journal ={Biomacromolecules},
volume={},
pages={1--1},
year=2025
}

David Grommisch*, Evelien Eenjes*, Maeve L Troost, Maria Genander
Epithelial architecture and signaling activity in the adult human esophagus.
Front Cell Dev Biol, 13 Art. No. 1632255 (2025)
Open Access PubMed Source   

Barrier epithelia function to shield the inside of our bodies from external stressors and pathogens. The esophageal epithelium is no exception, providing protection while at the same time transporting food to the stomach. Although many epithelial tissues are comparable between humans and mice, the human esophageal epithelium displays unique features in both progenitor cell organization and tissue architecture compared to the mouse. These differences have limited our understanding of the adult human esophagus, hindering the development of therapeutic strategies targeting human esophageal disease. Herein, we contrast the esophageal epithelial architecture and progenitor cell populations in mice and humans and discuss the role of a tentative human-specific progenitor cell population located in the submucosal gland ducts. Furthermore, we review current models available to study the human esophageal epithelium, focusing predominantly on adult primary organoids and epithelioids as well as the generation of human developmental esophageal epithelial cells from induced pluripotent stem cells. Finally, we discuss signaling activity implicated in maintaining normal human epithelial homeostasis, and how these pathways contribute to disease development. We aim to provide a comprehensive outlook on our current understanding of the human esophageal epithelium, while simultaneously highlighting unanswered questions in esophageal epithelial maintenance.
@article{Grommisch9034,
author={David Grommisch, Evelien Eenjes, Maeve L Troost, Maria Genander},
title={Epithelial architecture and signaling activity in the adult human esophagus.},
journal ={Frontiers in cell and developmental biology},
volume={13},
pages={null--null},
year=2025
}

Yu Meng, Szabolcs Horvát, Carl D. Modes#, Pierre A. Haas#
Impossible ecologies: Interaction networks and stability of coexistence in ecological communities.
Cell Syst, 16(7) Art. No. 101297 (2025)
Open Access PubMed Source   

Does an ecological community allow stable species coexistence? Identifying the general effects of competitive, mutualistic, and predator-prey interactions on stability remains a central problem of systems ecology because established approaches cannot account for the full network arrangement of these interactions. Here, we therefore analyze all interaction networks of N≤5 species with Lotka-Volterra dynamics by combining exact results and numerical exploration. We find that a very small subset of these networks is "impossible ecologies," in which stable coexistence is non-trivially impossible. We prove that the possibility of stable coexistence is determined by similarly rare "irreducible ecologies." Statistical sampling shows that this probability varies over orders of magnitude even in ecologies that differ only in the network arrangement of identical interactions. Thus, our approach reveals that the full network structure of interactions can influence stability of coexistence more than the established effect of interaction-type proportions. A record of this paper's transparent peer review process is included in the supplemental information.
@article{Meng9018,
author={Yu Meng, Szabolcs Horvát, Carl D. Modes, Pierre A. Haas},
title={Impossible ecologies: Interaction networks and stability of coexistence in ecological communities.},
journal ={Cell systems},
volume={16},
issue ={7},
pages={null--null},
year=2025
}

Kevin Nzumbi Mutemi, Oleg Simakov#, Leslie Pan, Luca Santangeli, Ryan Wesley Null, Mette Handberg-Thorsager, Bruno C Vellutini, Kevin A. Peterson, Bastian Fromm, Tomas Larsson, Emily Savage, Mireia Osuna Lopez, Rajna Hercog, Jan Provaznik, Diana Ordoñez-Rueda, Nayara Azevedo, Eve Gazave, Michel Vervoort, Pavel Tomancak, Wenhua Tan, Sylke Winkler, Vladimir Benes, Jerome Hui, Conrad Helm, B Duygu Özpolat#, Detlev Arendt#
A genome resource for the marine annelid Platynereis spp.
BMC Genomics, 26(1) Art. No. 665 (2025)
Open Access PubMed Source   

The marine annelid Platynereis dumerilii is a model organism used in many research areas including evolution and development, neurobiology, ecology and regeneration. Here we present the genomes of P. dumerilii (laboratory culture reference and a single individual assembly) and of the closely related P. massiliensis and P. megalops (single individual assembly) to facilitate comparative genomic approaches and help explore Platynereis biology. We used long-read sequencing technology and chromosomal-conformation capture along with extensive transcriptomic resources to obtain and annotate a draft genome assembly of ~ 1.47 Gbp for P. dumerilii, of which more than half represent repeat elements. We predict around 29,000 protein-coding genes, with relatively large intron sizes, over 38,000 non-coding genes, and 105 miRNA loci. We further explore the high genetic variation (~ 3% heterozygosity) within the Platynereis species complex. Gene ontology reveals the most variable loci to be associated with pigmentation, development and immunity. The current work sets the stage for further development of Platynereis genomic resources.
@article{Mutemi9029,
author={Kevin Nzumbi Mutemi, Oleg Simakov, Leslie Pan, Luca Santangeli, Ryan Wesley Null, Mette Handberg-Thorsager, Bruno C Vellutini, Kevin A. Peterson, Bastian Fromm, Tomas Larsson, Emily Savage, Mireia Osuna Lopez, Rajna Hercog, Jan Provaznik, Diana Ordoñez-Rueda, Nayara Azevedo, Eve Gazave, Michel Vervoort, Pavel Tomancak, Wenhua Tan, Sylke Winkler, Vladimir Benes, Jerome Hui, Conrad Helm, B Duygu Özpolat, Detlev Arendt},
title={A genome resource for the marine annelid Platynereis spp.},
journal ={BMC genomics},
volume={26},
issue ={1},
pages={null--null},
year=2025
}

Rimvile Prokarenkaite, Karolina Kuodyte, Greta Gudoityte, Elzbieta Budginaite, Daniel Naumovas, Egle Strainiene, Kristijonas Velickevicius, Audrius Dulskas, Ernestas Sileika, Jonas Venius, Virginijus Tunaitis, Augustas Pivoriunas, Vytaute Starkuviene, Vaidotas Stankevicius#, Kestutis Suziedelis#
PARP9-PARP13-PARP14 axis tunes colorectal cancer response to radiotherapy.
J Exp Clin Cancer Res, 44(1) Art. No. 199 (2025)
Open Access PubMed Source   

Colorectal cancer (CRC) is the third most prevalent cancer worldwide. Despite substantial advancements in CRC therapy in recent years, ionizing radiation (IR) continues to be the predominant treatment for colon malignances. However, it still lacks the precision required for excellent therapeutic outcomes, ultimately resulting in tumor radioresistance. This study seeks to explore the potential of atypical PARPs including PARP9, PARP12, PARP13 and PARP14 as innovative radiosensitizing targets for CRC.
@article{Prokarenkaite9035,
author={Rimvile Prokarenkaite, Karolina Kuodyte, Greta Gudoityte, Elzbieta Budginaite, Daniel Naumovas, Egle Strainiene, Kristijonas Velickevicius, Audrius Dulskas, Ernestas Sileika, Jonas Venius, Virginijus Tunaitis, Augustas Pivoriunas, Vytaute Starkuviene, Vaidotas Stankevicius, Kestutis Suziedelis},
title={PARP9-PARP13-PARP14 axis tunes colorectal cancer response to radiotherapy.},
journal ={Journal of experimental & clinical cancer research : CR},
volume={44},
issue ={1},
pages={null--null},
year=2025
}

Vera Schmiedhofer, Julian Sommersguter-Wagner, Oskar Knittelfelder, Helmut Jungwirth, Gerald N Rechberger, Didac Carmona-Gutierrez, Patrick Rockenfeller, Christoph Ruckenstuhl#, Frank Madeo#
Sugar accelerates chronological aging in yeast via ceramides.
Cell Stress Chaperones, 9(1) 158-173 (2025)
Open Access Source Full Text   

High carbohydrate intake, a characteristic of many Western diets, is a major contributor to age-associated pathologies. Here, we explored the molecular consequences of sugar overload during chronological aging in the yeast Saccharomyces cerevisiae. High levels of glucose and fructose resulted in a decrease of chronological lifespan as well as an increase of cell death, ROS and neutral lipids. Interestingly, these changes were accompanied by significantly altered ceramide profiles. Deletion of either the kinase Tort, a master regulator of growth and autophagy in response to nutrients, or the vacuole-anchored receptor Vac8, an important player in various autophagy pathways, improved survival and normalized ceramide profiles. This suggests that ceramides might play a role in sugar stress-induced cell death. In line, pharmacological inhibition of sphingolipid synthesis normalized ceramide profiles and improved chronological lifespan, whereas pharmacologically induced ceramide accumulation decreased chronological lifespan. In sum, our findings causally link nutrient signaling and an altered ceramide profile to sugar cytotoxicity in aging yeast, providing a basis for further search of feasible interventions against sugar-induced cell death.
@article{Schmiedhofer9032,
author={Vera Schmiedhofer, Julian Sommersguter-Wagner, Oskar Knittelfelder, Helmut Jungwirth, Gerald N Rechberger, Didac Carmona-Gutierrez, Patrick Rockenfeller, Christoph Ruckenstuhl, Frank Madeo},
title={Sugar accelerates chronological aging in yeast via ceramides.},
journal ={Cell stress & chaperones},
volume={9},
issue ={1},
pages={158--173},
year=2025
}
* joint first authors, # joint corresponding authors