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Luis David Garcia Puente, Elizabeth Gross, Heather A Harrington, Matthew Johnston, Nicolette Meshkat, Mercedes Perez Millan, Anne Shiu
Absolute concentration robustness: Algebra and geometry.
J SYMB COMPUT, 128 Art. No. 102398 (2025)
Open Access Source   

Motivated by the question of how biological systems maintain homeostasis in changing environments, Shinar and Feinberg introduced in 2010 the concept of absolute concentration robustness (ACR). A biochemical system exhibits ACR in some species if the steady-state value of that species does not depend on initial conditions. Thus, a system with ACR can maintain a constant level of one species even as the initial condition changes. Despite a great deal of interest in ACR in recent years, the following basic question remains open: How can we determine quickly whether a given biochemical system has ACR? Although various approaches to this problem have been proposed, we show that they are incomplete. Accordingly, we present new methods for deciding ACR, which harness computational algebra. We illustrate our results on several biochemical signaling networks.
@article{Puente8861,
author={Luis David Garcia Puente, Elizabeth Gross, Heather A Harrington, Matthew Johnston, Nicolette Meshkat, Mercedes Perez Millan, Anne Shiu},
title={Absolute concentration robustness: Algebra and geometry.},
journal ={Journal of Symbolic Computation },
volume={128},
pages={1--1},
year=2025
}

Daxiao Sun#, Xueping Zhao, Tina Wiegand, Cécilie Martin-Lemaitre, Tom Borianne, Lennart Kleinschmidt, Stephan W. Grill, Anthony Hyman, Christoph A. Weber#, Alf Honigmann#
Assembly of tight junction belts by ZO1 surface condensation and local actin polymerization.
Dev Cell, Art. No. doi: 10.1016/j.devcel.2024.12.012 (2025)
Open Access PubMed Source   

Tight junctions play an essential role in sealing tissues, by forming belts of adhesion strands around cellular perimeters. Recent work has shown that the condensation of ZO1 scaffold proteins is required for tight junction assembly. However, the mechanisms by which junctional condensates initiate at cell-cell contacts and elongate around cell perimeters remain unknown. Combining biochemical reconstitutions and live-cell imaging of MDCKII tissue, we found that tight junction belt formation is driven by adhesion receptor-mediated ZO1 surface condensation coupled to local actin polymerization. Adhesion receptor oligomerization provides the signal for surface binding and local condensation of ZO1 at the cell membrane. Condensation produces a molecular scaffold that selectively enriches junctional proteins. Finally, ZO1 condensates directly facilitate local actin polymerization and filament bundling, driving the elongation into a continuous tight junction belt. More broadly, our work identifies how cells couple surface condensation with cytoskeleton organization to assemble and structure adhesion complexes.
@article{Sun8882,
author={Daxiao Sun, Xueping Zhao, Tina Wiegand, Cécilie Martin-Lemaitre, Tom Borianne, Lennart Kleinschmidt, Stephan W. Grill, Anthony Hyman, Christoph A. Weber, Alf Honigmann},
title={Assembly of tight junction belts by ZO1 surface condensation and local actin polymerization.},
journal ={Developmental cell},
volume={},
pages={1--1},
year=2025
}

Anne Grapin-Botton#, Jonathan Y-H Loh#
Editorial overview: Regaining architecture and cell cross-talk upon regeneration.
Curr Opin Genet Dev, 91 Art. No. 102302 (2025)
PubMed Source  

@article{Grapin-Botton8881,
author={Anne Grapin-Botton, Jonathan Y-H Loh},
title={Editorial overview: Regaining architecture and cell cross-talk upon regeneration.},
journal ={Current opinion in genetics & development},
volume={91},
pages={null--null},
year=2025
}

Helen M Byrne#, Heather A Harrington#, Alexey Ovchinnikov#, Gleb Pogudin#, Hamid Rahkooy#, Pedro Soto#
Algebraic identifiability of partial differential equation models
NONLINEARITY, 38(2) Art. No. 025022 (2025)
Open Access Source   

Differential equation models are crucial to scientific processes across many disciplines, and the values of model parameters are important for analyzing the behaviour of solutions. Identifying these values is known as a parameter estimation, a type of inverse problem, which has applications in areas that include industry, finance and biomedicine. A parameter is called globally identifiable if its value can be uniquely determined from the input and output functions. Checking the global identifiability of model parameters is a useful tool when exploring the well-posedness of a given model. This problem has been intensively studied for ordinary differential equation models, where theory, several efficient algorithms and software packages have been developed. A comprehensive theory for PDEs has hitherto not been developed due to the complexity of initial and boundary conditions. Here, we provide theory and algorithms, based on differential algebra, for testing identifiability of polynomial PDE models. We showcase this approach on PDE models arising in the sciences.
@article{Byrne8898,
author={Helen M Byrne, Heather A Harrington, Alexey Ovchinnikov, Gleb Pogudin, Hamid Rahkooy, Pedro Soto},
title={Algebraic identifiability of partial differential equation models},
journal ={NONLINEARITY},
volume={38},
issue ={2},
pages={null--null},
year=2025
}

Thomas Brown, Ketan Mishra, Ahmed Elewa, Svetlana Iarovenko, Elaiyaraja Subramanian, Alberto Joven Araus, Andreas Petzold, Bastian Fromm, Marc R Friedländer, Lennart Rikk, Miyuki Suzuki, Ken-Ichi T Suzuki, Toshinori Hayashi, Atsushi Toyoda, Catarina Oliveira, Ekaterina Osipova, Nicholas D Leigh#, Maximina H Yun#, András Simon#
Chromosome-scale genome assembly reveals how repeat elements shape non-coding RNA landscapes active during newt limb regeneration.
Cell Genom, 5(2) Art. No. 100761 (2025)
Open Access PubMed Source   

Newts have large genomes harboring many repeat elements. How these elements shape the genome and relate to newts' unique regeneration ability remains unknown. We present here the chromosome-scale assembly of the 20.3 Gb genome of the Iberian ribbed newt, Pleurodeles waltl, with a hitherto unprecedented contiguity and completeness among giant genomes. Utilizing this assembly, we demonstrate conserved synteny as well as genetic rearrangements, such as in the major histocompatibility complex locus. We provide evidence suggesting that intronic repeat elements drive newt-specific circular RNA (circRNA) biogenesis and show their regeneration-specific expression. We also present a comprehensive in-depth annotation and chromosomal mapping of microRNAs, highlighting genomic expansion profiles as well as a distinct regulatory pattern in the regenerating limb. These data reveal links between repeat elements, non-coding RNAs, and adult regeneration and provide key resources for addressing developmental, regenerative, and evolutionary principles.
@article{Brown8894,
author={Thomas Brown, Ketan Mishra, Ahmed Elewa, Svetlana Iarovenko, Elaiyaraja Subramanian, Alberto Joven Araus, Andreas Petzold, Bastian Fromm, Marc R Friedländer, Lennart Rikk, Miyuki Suzuki, Ken-Ichi T Suzuki, Toshinori Hayashi, Atsushi Toyoda, Catarina Oliveira, Ekaterina Osipova, Nicholas D Leigh, Maximina H Yun, András Simon},
title={Chromosome-scale genome assembly reveals how repeat elements shape non-coding RNA landscapes active during newt limb regeneration.},
journal ={Cell genomics},
volume={5},
issue ={2},
pages={null--null},
year=2025
}

Bernhard Bein*, Ioannis Chrysostomakis*, Larissa Souza Arantes, Tom Brown, Charlotte Gerheim, Tilman Schell, Clément Schneider, Evgeny Leushkin, Zeyuan Chen, Julia Sigwart, Vanessa Gonzalez, Nur Leena W S Wong, Fabricio R Santos, Mozes P K Blom, Frieder Mayer, Camila J Mazzoni, Astrid Böhne, Sylke Winkler, Carola Greve, Michael Hiller
Long-read sequencing and genome assembly of natural history collection samples and challenging specimens.
Genome Biol, 26(1) Art. No. 25 (2025)
Open Access PubMed Source   

Museum collections harbor millions of samples, largely unutilized for long-read sequencing. Here, we use ethanol-preserved samples containing kilobase-sized DNA to show that amplification-free protocols can yield contiguous genome assemblies. Additionally, using a modified amplification-based protocol, employing an alternative polymerase to overcome PCR bias, we assemble the 3.1 Gb maned sloth genome, surpassing the previous 500 Mb protocol size limit. Our protocol also improves assemblies of other difficult-to-sequence molluscs and arthropods, including millimeter-sized organisms. By highlighting collections as valuable sample resources and facilitating genome assembly of tiny and challenging organisms, our study advances efforts to obtain reference genomes of all eukaryotes.
@article{Bein8911,
author={Bernhard Bein, Ioannis Chrysostomakis, Larissa Souza Arantes, Tom Brown, Charlotte Gerheim, Tilman Schell, Clément Schneider, Evgeny Leushkin, Zeyuan Chen, Julia Sigwart, Vanessa Gonzalez, Nur Leena W S Wong, Fabricio R Santos, Mozes P K Blom, Frieder Mayer, Camila J Mazzoni, Astrid Böhne, Sylke Winkler, Carola Greve, Michael Hiller},
title={Long-read sequencing and genome assembly of natural history collection samples and challenging specimens.},
journal ={Genome biology},
volume={26},
issue ={1},
pages={null--null},
year=2025
}

Christoph Zechner#, Frank Jülicher#
Concentration buffering and noise reduction in non-equilibrium phase-separating systems.
Cell Syst, Art. No. doi: 10.1016/j.cels.2025.101168 (2025)
Open Access PubMed Source   

Biomolecular condensates have been proposed to buffer intracellular concentrations and reduce noise. However, concentrations need not be buffered in multicomponent systems, leading to a non-constant saturation concentration (csat) when individual components are varied. Simplified equilibrium considerations suggest that noise reduction might be closely related to concentration buffering and that a fixed saturation concentration is required for noise reduction to be effective. Here, we present a theoretical analysis to demonstrate that these suggestions do not apply to mesoscopic fluctuating systems. We show that concentration buffering and noise reduction are distinct concepts, which cannot be used interchangeably. We further demonstrate that concentration buffering and a constant csat are neither necessary nor sufficient for noise reduction to be effective. Clarity about these concepts is important for studying the role of condensates in controlling cellular noise and for the interpretation of concentration relationships in cells. A record of this paper's transparent peer review process is included in the supplemental information.
@article{Zechner8896,
author={Christoph Zechner, Frank Jülicher},
title={Concentration buffering and noise reduction in non-equilibrium phase-separating systems.},
journal ={Cell systems},
volume={},
pages={null--null},
year=2025
}

Leon Hilgers#, Shenglin Liu, Axel Jensen, Thomas Brown, Trevor Cousins, Regev Schweiger, Katerina Guschanski, Michael Hiller#
Avoidable false PSMC population size peaks occur across numerous studies.
Curr Biol, Art. No. doi: 10.1016/j.cub.2024.09.028 (2025)
Open Access PubMed Source   

Inferring historical population sizes is key to identifying drivers of ecological and evolutionary change and crucial to predicting the future of species on our rapidly changing planet. The pairwise sequentially Markovian coalescent (PSMC) method provided a revolutionary framework to reconstruct species' demographic histories over millions of years based on the genome sequence of a single individual. Here, we detected and solved a common artifact in PSMC and related methods: recent population peaks followed by population collapses. Combining real and simulated genomes, we show that these peaks do not represent true population dynamics. Instead, ill-set default parameters cause false peaks in our own and published data, which can be avoided by adjusting parameter settings. Furthermore, we show that certain changes in population structure can cause similar patterns. Newer methods, like Beta-PSMC, perform better but do not always avoid this artifact. Our results suggest testing multiple parameters that split the first time window before interpreting recent population peaks followed by collapses and call for the development of robust methods.
@article{Hilgers8897,
author={Leon Hilgers, Shenglin Liu, Axel Jensen, Thomas Brown, Trevor Cousins, Regev Schweiger, Katerina Guschanski, Michael Hiller},
title={Avoidable false PSMC population size peaks occur across numerous studies.},
journal ={Current biology : CB},
volume={},
pages={1--1},
year=2025
}

Yitong Xu, Anna Chao, Melissa Rinaldin, Alison Kickuth, Jan Brugués, Stefano Di Talia
The cell cycle oscillator and spindle length set the speed of chromosome separation in Drosophila embryos.
Curr Biol, 35(3) 655-664 (2025)
PubMed Source   

Anaphase is tightly controlled spatiotemporally to ensure proper separation of chromosomes.1,2,3 The mitotic spindle, the self-organized microtubule structure driving chromosome segregation, scales in size with the available cytoplasm.4,5,6,7 Yet, the relationship between spindle size and chromosome movement remains poorly understood. Here, we address this relationship during the cleavage divisions of the Drosophila blastoderm. We show that the speed of chromosome separation gradually decreases during the four nuclear divisions of the blastoderm. This reduction in speed is accompanied by a similar reduction in spindle length, ensuring that these two quantities are tightly linked. Using a combination of genetic and quantitative imaging approaches, we find that two processes contribute to controlling the speed at which chromosomes move in anaphase: the activity of molecular motors important for microtubule depolymerization and sliding and the cell cycle oscillator. Specifically, we found that the levels of multiple kinesin-like proteins important for microtubule depolymerization, as well as kinesin-5, contribute to setting the speed of chromosome separation. This observation is further supported by the scaling of poleward flux rate with the length of the spindle. Perturbations of the cell cycle oscillator using heterozygous mutants of mitotic kinases and phosphatases revealed that the duration of anaphase increases during the blastoderm cycles and is the major regulator of chromosome velocity. Thus, our work suggests a link between the biochemical rate of mitotic exit and the forces exerted by the spindle. Collectively, we propose that the cell cycle oscillator and spindle length set the speed of chromosome separation in anaphase.
@article{Xu8885,
author={Yitong Xu, Anna Chao, Melissa Rinaldin, Alison Kickuth, Jan Brugués, Stefano Di Talia},
title={The cell cycle oscillator and spindle length set the speed of chromosome separation in Drosophila embryos.},
journal ={Current biology : CB},
volume={35},
issue ={3},
pages={655--664},
year=2025
}

Ariadna E Morales, Yue Dong, Thomas Brown, Kaushal Baid, Dimitrios-Georgios Kontopoulos, Victoria Gonzalez, Zixia Huang, Alexis-Walid Ahmed, Arkadeb Bhuinya, Leon Hilgers, Sylke Winkler, Graham M Hughes, Xiaomeng Li, Ping Lu, Yixin Yang, Bogdan Kirilenko, Paolo Devanna, Tanya M Lama, Yomiran Nissan, Martin Pippel, Liliana M Dávalos, Sonja Vernes, Sébastien J Puechmaille, Stephen J Rossiter, Yossi Yovel, Joseph B Prescott, Andreas Kurth, David A Ray, Burton K Lim, Eugene W Myers, Emma Teeling, Arinjay Banerjee, Aaron T Irving#, Michael Hiller#
Bat genomes illuminate adaptations to viral tolerance and disease resistance.
Nature, 638(8050) 449-458 (2025)
Open Access PubMed Source   

Zoonoses are infectious diseases transmitted from animals to humans. Bats have been suggested to harbour more zoonotic viruses than any other mammalian order1. Infections in bats are largely asymptomatic2,3, indicating limited tissue-damaging inflammation and immunopathology. To investigate the genomic basis of disease resistance, the Bat1K project generated reference-quality genomes of ten bat species, including potential viral reservoirs. Here we describe a systematic analysis covering 115 mammalian genomes that revealed that signatures of selection in immune genes are more prevalent in bats than in other mammalian orders. We found an excess of immune gene adaptations in the ancestral chiropteran branch and in many descending bat lineages, highlighting viral entry and detection factors, and regulators of antiviral and inflammatory responses. ISG15, which is an antiviral gene contributing to hyperinflammation during COVID-19 (refs. 4,5), exhibits key residue changes in rhinolophid and hipposiderid bats. Cellular infection experiments show species-specific antiviral differences and an essential role of protein conjugation in antiviral function of bat ISG15, separate from its role in secretion and inflammation in humans. Furthermore, in contrast to humans, ISG15 in most rhinolophid and hipposiderid bats has strong anti-SARS-CoV-2 activity. Our work reveals molecular mechanisms that contribute to viral tolerance and disease resistance in bats.
@article{Morales8892,
author={Ariadna E Morales, Yue Dong, Thomas Brown, Kaushal Baid, Dimitrios-Georgios Kontopoulos, Victoria Gonzalez, Zixia Huang, Alexis-Walid Ahmed, Arkadeb Bhuinya, Leon Hilgers, Sylke Winkler, Graham M Hughes, Xiaomeng Li, Ping Lu, Yixin Yang, Bogdan Kirilenko, Paolo Devanna, Tanya M Lama, Yomiran Nissan, Martin Pippel, Liliana M Dávalos, Sonja Vernes, Sébastien J Puechmaille, Stephen J Rossiter, Yossi Yovel, Joseph B Prescott, Andreas Kurth, David A Ray, Burton K Lim, Eugene W Myers, Emma Teeling, Arinjay Banerjee, Aaron T Irving, Michael Hiller},
title={Bat genomes illuminate adaptations to viral tolerance and disease resistance.},
journal ={Nature},
volume={638},
issue ={8050},
pages={449--458},
year=2025
}
* joint first authors, # joint corresponding authors