Publications
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NewtonBioMorphX: A computational framework for simulating tissue-scale mechanics of morphogenesis
2026
Computer Physics
Authors: Jahanbakhsh E., Milinkovitch M.
The self-organised morphogenesis of multicellular organisms emerges not only from biochemical but also from mechanical processes operating across spatial scales. Yet, computational tools for simulating tissue-scale mechanics have largely been released as restricted, study-specific codes. Here, we present NewtonBioMorphX, a GPU-accelerated, open-access comprehensive framework for simulating tissue-scale mechanical morphogenesis. Built on a finite-strain finite-element formulation on tetrahedral meshes, the software implements an unusually broad set of mechanical ingredients: isotropic and anisotropic (direction-specific) growth; multi-layer tissue mechanics; neo-Hookean hyperelasticity combined with stretch-based plasticity; Kelvin–Voigt viscoelasticity; passive anisotropic fibres emulating 3D collagen networks; anisotropic active contractile filaments emulating actin; Hertzian contact forces; and multiple orthonormal coordinate bases (Cartesian, normal–tangent, cylindrical, spherical, cone-adapted, and toroidal). Equally central is an extensive, user-friendly graphical interface spanning the entire workflow — mesh generation from geometric primitives or arbitrary mesh input, per-layer material and growth specification (including analytical functions of space and time compiled at runtime), boundary-condition assignment, real-time colour-mapped and glyph-based visualisation of scalar and tensor fields, and structured data export — allowing intricate mechanical modelling of morphogenetic processes without editing or recompiling source code. The NewtonBioMorphX framework is validated using a benchmark implementing the well-known Cook’s membrane problem, and its versatility is illustrated through parameter gradient plots, as well as twelve ready-to-run preset examples spanning diverse morphologies.
Scientific Reports
Authors: Lintner, M., Golen, J., Gawin-Grebla, A., Cavanaugh, C., Cyran, N., Holzmann, M., Wanek, W., Tyszka, J.
In this study, we investigated the feeding behavior of deformed and normal benthic foraminifera (Protista, Rhizaria) of the species Ammonia veneta. The degree of deformation was visualized by scanning electron and light microscopy. Food uptake and assimilation were quantified in undeformed, slight deformed (1–3 abnormal chambers), and heavy deformed (irregular coiling) individuals using isotopic labeling and confocal microscopy. Specimens were collected from the Belle Isle Marsh (Boston, USA) and maintained under controlled laboratory conditions. After a three-day incubation, slight deformed individuals showed food uptake and isotopic enrichment comparable to undeformed specimens. In contrast, heavy deformed foraminifera exhibited significantly reduced carbon and nitrogen assimilation, as well as a lower number of ingested food particles. Confocal observations further indicated reduced food processing in heavy deformed individuals. These results demonstrate that pronounced morphological deformities are associated with impaired feeding and assimilation performance. Our findings highlight that severe test deformation can substantially affect physiological functioning and should be carefully considered when selecting specimens for laboratory experiments or observing them in polluted areas.
Current biology : CB
Authors: Lago Solis B., Koch R., Nagoshi E.
Despite the progress in understanding the circadian pacemaker, the specific mechanism by which it regulates sleep remains incompletely understood. We have previously demonstrated that a substantial number of genes are rhythmically expressed in the mushroom body (MB) Kenyon cells (KCs), including Pka-C1, which encodes the catalytic subunit of protein kinase A (PKA). PKA-C1 plays a crucial role in promoting daytime wakefulness; however, the underlying mechanism remains elusive. Here, using a newly developed in vivo luciferase reporter, we show that the γ lobe is the primary site of rhythmic Pka-C1 expression. Through a combination of in silico analysis, CRISPR mutagenesis, and chromatin immunoprecipitation, we identify the transcription factor Onecut as a regulator of Pka-C1 transcriptional rhythms in γ-KCs. Furthermore, genetic trans-synaptic connectivity mapping and neuronal activity imaging reveal that the dorsal lateral clock neurons (LNds) provide inhibitory input to a subset of dopaminergic (DA) neurons in the protocerebral anterior medial (PAM) cluster, PAM-γ5, rhythmically modulating their activity. This, in turn, rhythmically activates MB γ-KCs via excitatory Dop1R signaling. Resulting γ-neuron activity rhythms drive Pka-C1 transcriptional rhythms through Onecut. Furthermore, these PKA-C1 rhythms reinforce neuronal activity rhythms, creating a feedback cycle between transcriptional and neural activity rhythms that promotes daytime wakefulness. Our findings highlight the conserved role of DA in promoting wakefulness and offer mechanistic insights into its complex regulation. More generally, this work provides a mechanistic framework for how circadian rhythms are translated into neural activity to orchestrate complex behaviors such as sleep.
ISME communications
Authors: Pinko D., Kenigsberg C., Levin S., Langlet D., Husnik F., Holzmann M., Abdu U., Abramovich S.
Symbiont-bearing benthic foraminifera, like corals, rely on endosymbionts for growth and nutrition and experience bleaching under heat stress. , found in tropical and subtropical waters, hosts a diverse range of endosymbionts belonging to Symbiodiniaceae. We examined the thermal tolerance of the Red Sea population, which is the source of an established, invasive population of in the Eastern Mediterranean. The Red Sea population is expected to exhibit enhanced thermotolerance, potentially due to its greater variety of endosymbionts. We conducted temperature-manipulation experiments, measuring calcification rates and net photosynthesis, evaluating the thermotolerance of and its endosymbionts. We also analyzed the diversity of Symbiodiniaceae by sequencing the internal transcribed spacer 2 (ITS2). Our results show that exposure to 35°C initially induced stress in the endosymbionts during the first week; however, net photosynthesis gradually recovered in subsequent weeks. In contrast, host calcification rates remained low at 35°C, though not completely inhibited. Amplicon sequencing revealed that by the end of the experiment, a single ITS2 type, belonging to Symbiodiniaceae and initially present in field-collected specimens, became dominant in cultured individuals. Because this type became dominant across all temperature treatments, the observed shift likely reflects a response to laboratory conditions rather than direct thermal selection. Consequently, although the recovery at 35°C is consistent with acclimatory physiological responses, it does not provide direct evidence for symbiont-specific acclimation. Our findings suggest that holobiont physiological recovery and symbiont shuffling under laboratory conditions may contribute to the resilience of in warming oceans.
Nature communications
Authors: Helleboid P., Tzika A.
The mechanisms by which novel differentiation pathways evolve to produce new cell types are still not fully understood. Chromatophores, the pigmented cells in the skin, offer an ideal paradigm because each type independently develops from neural crest cells to produce a distinct colour using well-characterised biosynthetic pathways. Here we show, using single-cell gene expression analyses, that canonical chromatophores develop in the embryonic skin of corn snakes and bearded dragon lizards. Yet, we identify previously undescribed chromatophore subtypes in the bearded dragon. These populations co-express progenitor and mature markers and possibly contribute to embryonic skin patterning, as revealed by whole-mount in situ hybridisation. Comparative analyses uncover that while mature chromatophores show cross-species similarity reflecting shared pigmentary function, progenitor states differ in transcription factor usage, including species-specific deployment of MITF, PAX7, and TFEC. Integration with teleost and amphibian datasets confirms that diversification of pigmentation arises through distinct progenitor trajectories converging on similar mature states.
Proceedings of the National Academy of Sciences of the United States of America
Authors: Ibrahimi M., Jahanbakhsh E., Tzika A., Milinkovitch M.
The spatial patterning of mammalian hair follicle precursors in embryonic skin is most commonly studied in the laboratory mouse (), where new follicles form equidistantly from preexisting ones in successive waves. This simple geometric rule has been effectively described as emerging from an expansion-induction process. However, such a description is incompatible with more recent developmental data indicating instead that scale, feather, and hair placodes self-organize through reaction-diffusion-chemotaxis cell interactions involving epidermal and dermal signaling. Here, we suggest that the chemotactic component of this framework suffices to describe the dynamics of placode insertion in two mammalian species that exhibit drastically different patterns. More specifically, we investigate a continuum dynamical model capturing interactions between motile dermal mesenchymal cells and an epidermal chemoattractant, embedded in a two-dimensional, isotropically expanding domain representing the growing embryonic skin. Through numerical simulations, mathematical analysis, and comparison to experimental developmental data, we first show that the chemotaxis model gives rise to the effective geometric rule that initially justified the development of the expansion-induction model in the laboratory mouse. Second, we show that the strikingly regular hair placode pattern in the spiny mouse ()-with long-range order, specific orientation and anisotropies-is not generated by an expansion-induction mechanism, but is recapitulated by an anisotropic chemotaxis model combined with experimentally observed anisotropic growth. Overall, our findings reveal that variation in the chemotactic component of the corresponding self-organizational system might be a key determinant of interspecific differences in hair placode patterning dynamics and resulting spatial organizations.
A defined community of core gut microbiota members promotes cognitive performance in honey bees
2026
PNAS
Authors: Cabirol A, Quinn A, Schafer J, Neuschwander N, Kesner L, Liberti J, Engel P.
Gut microbiota across animals have been shown to influence host cognition and behavior. However, it remains unclear whether these cognitive effects are driven by specific bacterial species or arise from community-level interactions. Here, we leveraged the honey bee (Apis mellifera) as a model system, which harbors a simple and well-characterized gut microbiota that is experimentally tractable and has been previously shown to impact host cognition. We established a defined bacterial community-composed of core members of the honey bee gut microbiota. Gnotobiotic bee experiments with the full community, communities missing individual members, or individual members showed that only the full community enhanced honey bees' performances in odor discrimination learning and short-term memory compared to microbiota-deprived bees. Metabolomic analyses identified several metabolites associated with learning success that mapped to pathways modulated by microbial colonization, including tryptophan metabolism, nucleoside metabolism, and lysine degradation. However, many of these metabolites were not altered by removing individual members from the full microbial community. This suggests that microbiota-mediated improvements in cognition are emergent properties of the community as a whole, rather than the result of individual metabolites or specific bacterial taxa acting alone. Our findings support a systems-level view of the microbiome, suggesting that understanding and manipulating host development, particularly in relation to brain function, should prioritize microbial community function (e.g., metabolic pathways) over taxonomic composition alone.
Characterization of the post-mating responses of Drosophila hydei, a species that lacks Sex-Peptide
2026
Communications biology
Authors: Revel M, Yildirim Z, Fabbro L, Nagoshi E, Maeda RK
Sex Peptide (SP) induces many of the most studied female post-mating responses (PMRs) in Drosophila melanogaster but has been lost multiple times in the Drosophila genus. We decided to explore the PMRs of Drosophila hydei, a species without SP. Our work shows that the PMRs in D. hydei are somewhat different than those found in D. melanogaster and may be the consequence of a selection for producing a reduced number of extremely long sperm. D. hydei females lack the substantial post-mating increase in egg production found in D. melanogaster, mostly displaying only a brief induction in the laying of stored eggs. Mated females do not show a reduction in lifespan that has been linked to changes in metabolism and egg production. To further explore the reproductive biology of this species, we performed sperm competition experiments that suggest that D. hydei females may select sperm based on characteristics linked to changes in seminal fluid proteins. This was further investigated by examining the structure of the seminal fluid-producing accessory glands and the egg laying PMRs in different Drosophila species. Finally, video-based monitoring of D. hydei females was used to uncover novel changes in circadian rhythm and light preference in mated females.
iScience
Authors: Agabiti C., Donato E., Setti E., Dagenais P., Milinkovitch M., Laschi C., Sabatini A., Mazzolai B., Falotico E.
The elephant trunk is a highly dexterous muscular hydrostat whose continuous, distributed deformations pose significant challenges for mathematical modeling. We introduce linear "stereotypical" laws that map desired trunk configurations, parameterized by curvature and length, directly to the internal muscle-analogue forces required in our rod-based dynamic model. The trunk is represented as a simplified multi-segment structure of point masses linked through longitudinal and radial muscle analogues and connective tissue, all modeled using rods. Using these laws, the model predicts biological reaching trajectories with tip-position errors below 8% while maintaining hydrostatic volume across trials. The resulting force-shape mappings reveal consistent, repeatable internal force patterns underlying trunk postures, providing a compact representation of actuation strategies that generate specific planar shapes. By reducing high-dimensional continuum dynamics to simple linear relationships, this framework preliminarily enables the inference of muscle-force distributions from shape configurations, laying the groundwork for deeper exploration of the elephant trunk motion strategies and their translation into advanced robotic systems control.
European journal of protistology
Authors: Siemensma F., Holzmann M.
Non-marine foraminifera remain among the least explored groups within the Rhizaria, despite their ecological and evolutionary significance. We report the rediscovery of the agglutinated monothalamid Limnogromia saxicola (Penard, 1905) and provide the first integrative morphological and molecular characterization of this species since its original description. In addition, we describe four new organic-walled monothalamids based on morphological and molecular data: Claparedellus arenivagus sp. nov., C. dunicola sp. nov., Perseforaminifer crypticus gen. et sp. nov., and Edaphoallogromia bettighoferi sp. nov. Morphological differentiation is challenging due to limited diagnostic characters and intraspecific variability, although nuclear architecture and birefringent cytoplasmic crystals provide useful markers. Limnogromia saxicola and P. crypticus include environmental sequences that are nearly identical to those obtained from individually extracted specimens. This is the first time that environmental sequences can be confidently linked to defined species. Additionally, brief descriptions and illustrations are provided for seven undetermined monothalamous morphotypes for which no sequences could be obtained. Our findings expand the known diversity, ecological range, and cryptic complexity of freshwater monothalamids. This study underscores the importance of integrating morphological, molecular, and ecological data to resolve taxonomy, detect cryptic diversity, and better understand the evolutionary history of non-marine monothalamids.
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