Philosophical Transactions of the Royal Society B: Biological Sciences
● The Royal Society
Preprints posted in the last 7 days, ranked by how well they match Philosophical Transactions of the Royal Society B: Biological Sciences's content profile, based on 72 papers previously published here. The average preprint has a 0.05% match score for this journal, so anything above that is already an above-average fit.
Niederbremer, C.; Dal Pesco, F.; Mundry, R.; Neumann, C.; Diakhate, N.; Fischer, J.
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Across different modalities, signals play a core role in attracting mates and influencing mating success. In several non-human primate species, females produce calls during mating that are thought to promote male competition over receptive females. The extent to which social system characteristics modulate the function of copulation calls remains less clear. We studied copulation calls in wild Guinea baboons (Papio papio), who live in a multilevel society structured around units in which females associate and mate almost exclusively with a single male. We hypothesised that females use copulation calls as an indirect form of mate competition, with competition increasing in larger units. In addition, we hypothesised that females are more likely to mate again after calling. We analysed 6116 copulations between 2014 and 2025, involving 99 reproductively active females and 78 subadult and adult males. Females produced copulation calls in 72.7% of copulations, with large inter-individual variation. Neither unit size nor its interaction with the female's swelling size or the presence of simultaneously receptive females affected the probability of calling. A survival analysis with a subset of the data (2353 copulations) revealed no effect of calling on the latency to the next mating. Our results render the hypothesis that female Guinea baboons use calls in indirect mate competition unlikely. Yet, the probability of calling varied with sexual swelling size, suggesting that calls signal female fertility. Possibly, Guinea baboon copulation calls represent an evolutionary remnant, no longer under selective pressure, and can be considered index signals of female fertility.
White, J. R.; Robinson, J. D.; Doremus, M. R.
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Heritable bacterial symbionts are pervasive in terrestrial arthropods, often imposing reproductive manipulations to promote their own spread within host populations. Co-infections are common, potentially allowing symbiont co-infectors to hitchhike through a host population. However, adverse thermal conditions can disrupt these communities, particularly when co-infectors vary in their thermal sensitivity. We used a multi-generation experiment to test whether warm (29 {degrees}C) conditions disrupted spread of heritable symbionts through uninfected populations of the spider, Mermessus fradeorum. We tested two common infection combinations: a single infection with a cytoplasmic incompatibility (CI) inducing Rickettsiella or a feminizing co-infection that included a feminizing Wolbachia, the same Rickettsiella, and up to three apparent hitchhikers (two additional Wolbachia strains and Tisiphia). We initiated replicate populations with 1/3 of one infection type and 2/3 uninfected spiders, evaluating population infection rate over 5 spider generations under different temperature regimes. Under cool (21{degrees}C) conditions, Wolbachia feminization drove co-infection to 88% and Rickettsiella CI drove single infection to 83% of host populations. Vertical transmission for all symbionts was high (97-99%) and hitchhiking symbionts also spread effectively. Under warm conditions, feminization and CI efficacy were reduced, and symbionts suffered variably reduced vertical transmission. Warm conditions ultimately destroyed the co-infecting symbiont consortium and impeded symbiont spread. On its own, though, Rickettsiella was still able to increase, despite reduced strength of CI. We hypothesize that contrasting tensions between feminizing spread of the symbiont consortium versus environmentally driven loss of function and transmission may explain observed patterns of mixed infections in field populations of this spider.
Shibasaki, S.
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Rapid evolution allows populations to persist in environments where they would otherwise go extinct. This phenomenon, known as evolutionary rescue, is typically studied in the framework of biological evolution, yet adaptive traits can also arise and spread through cultural evolution. The present study developed a stochastic eco-evolutionary model to compare rescue probabilities through biological and cultural evolution. Transmission bias governed the rescue probability under cultural evolution by setting how readily a rare adaptive trait was copied. Conformity bias suppressed population persistence because a rare trait was the least likely to be copied. Content bias toward the adaptive trait enabled evolutionary rescue when social learning was rapid, but it typically yielded a lower rescue probability than biological evolution. Only anticonformity bias, together with a high social learning rate, exceeded the rescue probability of biological evolution by enabling the adaptive trait to be established more rapidly. These results demonstrate that transmission bias alters the demographic consequences of cultural evolution and highlight the importance of transmission processes in evolutionary rescue theory. Understanding how adaptive behaviours are socially transmitted may also improve predictions of animal population persistence and inform conservation efforts in rapidly changing environments.
Pryymachenko, Y.; Wilson, R.; Abbott, J. H.
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Objectives To analyse the long-term effects of a cruciate ligament (CL) injury on health and socioeconomic outcomes. Methods We used a comprehensive national injury insurance database to identify CL injuries occurring in New Zealand between 2009 and 2022, and employed a doubly robust staggered difference-in-differences research design to identify the effects of these injuries on outcomes up to 10 years after injury. The outcomes of interest were healthcare use (hospitalisations, emergency department visits, medications, knee replacement surgery for osteoarthritis), associated healthcare costs, and labour market outcomes (employment rates, income, and government benefit payments). Results We identified 61 344 CL injuries for inclusion in the analysis. Over 10-year follow-up, a CL injury resulted in increased healthcare use (0.6 more hospitalizations [95%CI 0.4 to 0.7], 1.7 more days spent in hospital [95%CI 1.3 to 2.1], 0.4 more emergency department visits [95%CI 0.3 to 0.6], 2.5 more outpatient visits [95%CI 1.8 to 3.2], and 4.7 more medications dispensed [95%CI -1.8 to 11.2]) and public healthcare costs ($7 537; 95%CI 5 888 to 9 186), reduced income (-$6 060; 95%CI -11 644 to -475), and increased benefit payments ($1 152; 95%CI 542 to 1 761). Conclusion CL injuries have long-term impacts on healthcare use and socioeconomic outcomes. Strategies to reduce the incidence of CL injuries have the potential to realise large health and economic benefits.
Byrne, H. A. M.; Hartley, M. E. H.; Perez, I.; Scotese, C. R.; Lunt, D. J.; Valdes, P. J.; Green, J. A. M.
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The ocean tides influence key Earth system processes at a range of spatial and temporal scales. It is known that the geometry of ocean basins is the leading controller of tidal energetics, so well-constrained palaeogeographic reconstructions and tidal properties for Earths past are imperative when investigating other Earth system processes. Here, we present a novel way to constrain both deep-time tidal model results and reconstructions, by combining palaeoecology with sedimentology. We compare new palaeo-tidal model simulations for the Cambrian period, significant for the early origin and radiation of major animal fauna, to tidal proxies. One of the most abundant soft-bodied organisms preserved during this time are cnidarian medusae (jellyfish). A total of 17 cnidarian medusae localities were obtained through the literature, which had an adequate global distribution and occurred at regular intervals throughout the period of study. In some locations there were also estimates of palaeo-tidal range. Our results show a good agreement between the simulations and proxy data. In the few locations where there is disagreement, it is proposed that the palaeogeographic reconstructions are missing details, e.g., island chains, and our results allow for the palaeogeographic reconstructions to be improved. The proxy method presented is promising and can be applied to other time-periods with different marine fossils, particularly at evolutionary and extinction periods where the marginal marine environment is of importance.
Baruah, G.; KC, Y. K.
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The shape of density-dependence governs species persistence, and ecosystem stability. Yet, whether per-capita growth declines sublinearily, or superlinearily with density remains hotly debated. Growth rates across the tree of life have been shown to decline sublinearly with density, whereas theory founded on resource competition predicts the opposite. Here, we resolve this discrepancy and show that sublinearity can readily emerge from geometric constraints on consumer interactions. By linking inter individual spacing, movement and interference rates, we derive two limiting-interference regimes, one of which the well-mixed limit recovers the form of classic Beddington DeAngelis interference response. We then developed an individual-based model from first principles which reproduces the derived sublinearity response, and further use empirical data from published consumer-resource experiments that also bears the signature of sublinear density-dependence. Further, embedding the interference mechanisms underlying the emergence of sublinear density-dependence in coexistence theory opens a new regime for species coexistence where classical theory fails to predict. Our framework indicates that non-consumptive interactions are not merely a correction to resource competition but might be a distinct axis along which diverse communities may potentially coexist.
Farr, E.; Kritikaki, E.; Chroscik, M.; Admane, C.; Graves, E.; Tudor, C.; Chan, H. M.; Boccacino, J.; McWilliam, J.; Torabi, F.; Chakala, K.; Basurto-Lozada, D.; Li, T.; Binkevich, A.; Predeus, A.; Prete, M.; Panamarova, M.; Adao, D.; Evans, K.; Stewart, K.; Steele, L.; Winheim, E.; Gopee, N. H.; Stephenson, E.; Patel, M.; Hale, C.; Gambardella, L.; Harpur, B.; Smith, C.; Horsfall, D.; Shanmugiah, V.; Parts, L.; Adams, D. J.; Kasper, M.; Dugourd, A.; Saez-Rodriguez, J.; Foster, A. R.; Haniffa, M.
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Single-cell technologies have generated cell censuses of tissues, however, how tissue geometry reflects functional needs remains poorly characterized. The human pilosebaceous unit offers a tractable model, a prenatally-formed complex mini-organ combining hair and sebum production with a stem cell reservoir. Using histomorphology, spatial transcriptomics, and single-cell multiomics on the same human prenatal scalp skin samples (8-19 post-conception weeks), integrated and analyzed using machine learning approaches, we built a spatiotemporal map of pilosebaceous unit development. We demonstrate that epithelial-mesenchymal interactions coordinate cellular fate and organogenesis, using an in vitro hair-bearing skin organoid model to validate this tissue-patterning. In addition, we show sebaceous gland developmental programmes are overcome during tumor formation. Our large-scale multi-modal analysis provides a unique framework for understanding form and function of tissues with applications in tissue engineering and pathology.
Yakubu, S.; Mousavi, S.; Eden, J.; Kabajulizi, J.; Palade, V.; Daneshkhah, A.
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Communities exposed to flooding can experience markedly different mental health outcomes, yet conventional resilience indicators capture only part of the social and contextual conditions that may explain this variation. This study develops a multilevel and predictive framework for examining community resilience and depressive symptoms following flood exposure in Indonesia. Data were drawn from 20,303 respondents aged 15 years and older nested within 312 communities in the Indonesia Family Life Survey (IFLS-5). Depressive symptoms were assessed using the 10-item Centre for Epidemiologic Studies Depression Scale (CES-D-10), with Rasch Partial Credit Model calibration used to examine measurement properties. Bayesian multilevel models quantified between-community heterogeneity and assessed how far observable structural resources accounted for this variation. Community resilience was represented through two complementary constructs: structural resilience, based on observable socioeconomic and social-capital resources, and Latent Community Protective Capacity (LCPC), a model-derived proxy for residual contextual variation in depressive-symptom risk. Approximately 6 percent of variation was attributable to between-community differences, while observable structural resources explained only part of this heterogeneity. Structural resilience and LCPC were weakly correlated (r = 0.155). Moderation analyses provided no clear evidence that structural resilience altered the flood-depression association, while LCPC showed a directionally consistent but uncertain buffering pattern. Predictive models incorporating community-level information improved discrimination, with the best-performing model reaching an ROC-AUC of approximately 0.71. The findings suggest that observable resource-based indices provide an incomplete account of community-level mental health vulnerability and that residual contextual measures may provide complementary information, while requiring cautious interpretation and independent validation.
Rajput, R.; Saha, L.; Ahmed, Z.; Naiker, P.; Do, L.; Bisset, A.; Hooper, C.
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High-phenolic plant genera present a major technical limitation in genomic research. Standard extraction approaches that perform reliably across diverse flora often perform poorly when applied to recalcitrant taxa, producing low DNA yield and integrity incompatible with sequencing requirements. The genus Anigozanthos (Kangaroo paws) from the family Haemodoraceae exemplifies this problem. We identified key physicochemical factors governing extraction failure in this genus and resolved them through targeted modifications to lysis chemistry and contaminant management. The resulting protocol achieved a near threefold improvement in DNA purity, substantially reducing contaminant carry over and consistently yielded high-integrity, long DNA fragments (DIN > 7) across a diverse sample set spanning cultivated and wild material across four diverse genera of Haemodoraceae. We also tested a straightforward purity assessment framework that can be implemented in any standard molecular laboratory, enabling rapid pre-submission quality assessment without the need for specialised equipment. Together these advances open a practical path to genomic characterisation of Anigozanthos that establishes a transferable model for genomic research across Australia ' s chemically complex native flora.
Yair, N.; Coldham, Y.; Tavor, I.; Bar-Haim, Y.
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Individuality is a defining feature of human biology. The functional network architecture of the human brain harbors person-specific qualities and forms individualized connectivity profiles that function as a neural fingerprint, both stable and unique across time. Here, using fMRI data from 431 Human Connectome Project participants, we examined whether neural individuality is more strongly exhibited in brain regions bearing signatures of recent human evolution. We calculated region-wise fingerprinting accuracy and associated it with four properties of evolutionary cortical organization: cortical expansion, myelin content estimate (T1w/T2w), human-specific gene-expression profiles, and functional homology to other primates. Across all four measures, neural individuality was strongest in cortical areas showing greater evolutionary novelty in humans, particularly frontoparietal control and default mode networks, and weaker in more conserved primary regions. Our findings connect evolutionary variation across species with stable functional variation among individuals.
Lustenhouwer, R.; Dijkerman, H. C.
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Tactile imagery has attracted growing fundamental and clinical interest. Previous studies often investigated neural and functional similarities between imagined and actual touch. Several functional aspects of touch, such as differences between active and passive touch, between different haptic features during active touch or sensitivity of different body parts for passive touch, have also been explored in tactile imagery. Furthermore, considerable individual differences in the ability to engage in tactile imagery have been observed. However, several important aspects, involving different imagery components and a wide variety of touch qualities remain to be explored within a single comprehensive study. The current study therefore aims to provide a wide-ranging assessment of tactile imagery in terms of imagery processing components (vividness, maintenance, transformation), type of touch (active versus passive) and touch qualities (object properties for active touch, different tactile sensations across body sites for passive touch). We developed a comprehensive questionnaire containing 72 items to assess tactile imagery ability. 136 healthy participants were asked to imagine different touch types and rate imagery vividness and their ability to maintain and transform each sensation on 5-point Likert-scales. Active touch varied by object (plastic bottle, modeling clay, sponge) and property (temperature, weight, texture, resistance). Passive touch varied by body site (lip, shin, sole of the foot, lower back) and sensation (stroking, vibration, pinching). Overall, participants were able to perform tactile imagery: the vast majority reported at least some imagery across touch types. Individual variability was substantial: scores bridged both ends of the scale. Active tactile imagery differed significantly between objects, depending on tactile property. Object-property pairs with particularly strong imagery were bottle-temperature, bottle-weight and sponge-texture, whereas bottle-resistance elicited weaker imagery, as did temperature and weight for both sponge and clay. Passive tactile imagery was significantly stronger for body sites with higher receptor density (i.e. lip and foot). Imagery of stroking was significantly weaker than vibration and pinching. Active and passive imagery showed a strong, positive correlation, though some participants had relatively strong active imagery, but weaker passive imagery, or vice versa. Our findings confirm that tactile imagery ability varies across individuals and touch types, underlining the importance of a comprehensive imagery ability assessment tool specific to the tactile domain.
Lopez-Idiaquez, D.; Satarkar, D.; Sheldon, B. C.
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Most evidence of the consequences of climate change in natural systems has focussed on shifts in mean temperature (1,2), but the effects of extreme climatic events (ECEs) remain far less understood. This is particularly true for very severe ECEs that may occur only once every few decades. Understanding the consequences of these severe events for natural populations is nonetheless critical, since their frequency is predicted to rise under current climate change (3). Here we combine a unique long-term dataset spanning almost five decades of breeding (>20,000 events) and morphological data (>120,000 observations) in adult and nestling great tits (Parus major) and blue tits (Cyanistes caeruleus) with fine-scale temperature records to examine the effects of an unprecedented heatwave in May 2026 on breeding success and morphology. Average temperature during the heatwave (22-29 May 2026) was 7.85 C above the historical record, reaching +10.5 C (+4.32 SD) at its peak (25-26 May). These record-breaking temperatures significantly reduced adult breeding success and nestling bmass relative to expectation in the absence of a heat-wave. Given the heatwave was widespread (Fig. 1A), our findings from a single, exceptionally well-studied population are likely to generalise to other species exposed to the same event, providing key evidence that severe ECEs can substantially harm wild populations.
Chandra, S.; Chouhan, S.; Behera, L.; Nandi, C. K.
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Anterograde and retrograde signalling establish bidirectional communication between the nucleus and chloroplasts. Retrograde signals from chloroplasts regulate nuclear gene expression while anterograde signals from the nucleus coordinate chloroplast development and maintain cellular homeostasis. How this bidirectional signalling framework extends beyond locus-specific regulation to shape the global spatial organization of nuclear chromatin across tissues remains unclear. Although anaesthesia can alter chromatin organisation, the role of chloroplast dysfunction in these changes remains unclear. Here, we investigate how chloroplast dysfunction and anaesthesia influence euchromatin and heterochromatin organisation in Solanum lycopersicum seedlings across tissues with contrasting photosynthetic competence. Using confocal and super-resolution radial fluctuation (SRRF) imaging with quantitative multiparameter analysis, we identify distinct, tissue-specific chromatin responses to chloroplast disruption and anaesthesia. Notably, anaesthesia induces distinct spatial chromatin changes across tissues that are independent of chloroplast dysfunction, suggesting a direct nuclear response to anaesthesia rather than a chloroplast-mediated retrograde effect. These findings highlight chromatin topology as a potential quantitative biomarker of cellular disruption and provide a framework for investigating anterograde chloroplast-nucleus coordination and stress-responsive nuclear organisation in plants.
Yamaguchi, K.; Uchida, K.; Hiraiwa, M.; Fukano, Y.
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Citizen science observations are abundant, but conservation requires turning uneven records into reliable predictions and directing new surveys to where information is missing. We developed a biodiversity platform for Japan that is updated monthly and integrates 2.32 million records to predict 8,297 species across seven taxonomic groups. Shared representation models outperformed species-specific models in four groups and extended predictions to species with few records. Five independent datasets, including structured monitoring, environmental DNA and complete forest inventories, confirmed that the models ranked observed species and occupied sites above alternatives, with median AUCs of 0.724 to 0.894 across sites and 0.650 to 0.841 across species. For any user-selected area, the platform returns candidate species, distribution predictions, a biodiversity map corrected for uneven observation effort, a conservation priority map for native species and a map recommending where to survey next. This map highlights places where species with few records are predicted to occur despite limited sampling. Independent observations showed that areas ranked highly by this predicted potential contained many such species, indicating that model predictions can help direct surveys toward knowledge gaps. New observations are incorporated into monthly updates, creating a national feedback system connecting citizen science, local conservation decisions and future surveys.
van Denderen, P. D.; Andersen, K. H.; Denechere, R.
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Squid abundance has been reported to increase globally between 1970 and 2010. This increase has been hypothesized to result from two primary factors: the loss of top predators due to overfishing and rising ocean temperatures. The decline in apex predators may lead to the expansion of squid populations either through reduced predation pressure or diminished competition with juvenile predators. Concurrently, increased temperatures could enhance the somatic growth rates of squid, thereby accelerating their population growth. However, empirically disentangling the impacts of predator loss and temperature on squid biomass remains challenging, especially in a food-web context. In this study, we used a size- and trait-based model of upper trophic levels that resolves the ecosystem structure -- biomass and trophic interactions of fish and squid -- for varying depth, temperature, and secondary production, to investigate two hypotheses of the historical expansion of squid, i.e., the effects of predator depletion from fishing and rising temperatures on squid biomass. Our model reveals that intensified fishing of squid predators -- specifically large demersal fish in shelf systems and large pelagic fish in open oceans -- leads to a slight increase in squid biomass. Conversely, elevated temperatures are associated with a decline in squid biomass. This temperature-driven reduction in biomass is attributed to an increased metabolism of squids beyond the available food supply. If historic overfishing on large marine predators continues to be curtailed, we expect a corresponding reduction in global squid biomass and fisheries potential, which could be further exacerbated by rising temperatures.
Gorstein, E.; Tang, M.; Bruzzone, H.; Solis-Lemus, C.
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Standard methods for ancestral sequence reconstruction (ASR) rely on substitution models for the residues in a biological sequence and assume independent evolution across these sites, ignoring the epistatic interactions that shape molecular evolution. In contrast, deep learning models like variational autoencoders (VAEs) can learn low-dimensional representations ("embeddings") of sequences in a protein family that may implicitly handle these dependencies, raising the possibility of performing more accurate ASR by interpolating between extant sequence embeddings within the VAE's latent space. In this study, we test this hypothesis by developing and evaluating a VAE-based ASR pipeline. Benchmarking this approach against established likelihood-based and parsimony methods using various simulations of protein evolution, including scenarios with and without epistasis, we find that the VAE-based approach is consistently and significantly outperformed by standard methods, even in epistatic regimes where it was hypothesized to have an advantage. We further show that this failure is not due to a lack of phylogenetic structure in the latent space, which does contain evolutionary signal. Rather, the primary limitation is the information loss inherent to the autoencoding process: the VAE's decoder cannot generate sequences with sufficient fidelity for the precise demands of ASR.
Desai, R.; Pople, D.; Musale, A.; Jain, S.; Sajjad, I.; Wittebort, R. J.; Koder, R. L.; Nanda, V.
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The folding thermodynamics of proteins are dominated by two opposing forces, the loss in backbone entropy and the packing of hydrophobic groups. The same forces are major contributors to the extension thermodynamics of elastic proteins with the distinction that both processes act in concert, favoring the higher chain and solvent entropy of a relaxed conformation. The relative entropic contributions specify the recoil mechanism; human elastin recoil is primarily driven by hydrophobic forces, whereas fly resilin has a rubber-like mechanism driven by backbone entropy. Despite the importance of elastic proteins to tissue biomechanics, few have been identified, let alone characterized to the same extent as elastin and resilin. We develop a thermodynamic framework that maps proteins by sequence-derived estimates of extension-induced backbone and solvent entropy changes. Putative elastic proteins are proposed and classified by recoil mechanism based on estimated thermodynamic features. Proteins that map to elastic regions are overrepresented by the skin proteome. The set of predicted elastic domains is further extended by incorporating sequence context embedded in protein language models. Protein domains with distinct thermodynamic recoil mechanisms cluster on the latent space manifold. Some of these domains are anticipated to have roles within molecular machines, expanding the scope of elastic protein function beyond mechanical materials like elastin and resilin.
Zhou, Y.; Gong, L.; Niu, G.; Shi, H.; Gutell, R.; Li, X.; Wei, M.
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Animal mitochondrial rRNAs are commonly viewed as structurally reduced, yet sponge mt SSU rRNAs range from compact to highly expanded structures. Using nine conserved structural anchors, we compared 216 taxonomically resolved records from four classes and 22 orders, including 16 freshwater Spongillida and 200 marine sponges. Twelve homologous hypervariable substructures were coded as structural types, and their ordered combinations as composite types. We identified 38 structural types and 62 composite types across molecules ranging from 853 to 2,019 nt. Hexactinellida and freshwater Spongillida were each uniform for a distinct composite type but differed markedly in overall structure: hexactinellid mt SSU rRNAs were compact, whereas those of Spongillida were long and contained four to five candidate insertion regions. These results show that a conserved scaffold can accommodate extensive lineage-associated structural variation and provide a practical framework for comparing highly divergent mitochondrial rRNAs.
Schoenit, A.; O'Byrne, J.; Daubech, C.; Schmidt, W.; Anger, L.; Shen, Y.; Ruebsam, M.; Dubrall, R.; Wodrascka, F.; Voituriez, R.; Ladoux, B.; Niessen, C. M.; Mege, R.-M.
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Delamination within stratified epithelia like the skin epidermis describes the detachment and upward motion of cells originating from the basal layer. Despite its fundamental importance for tissue development, homeostatic regeneration and repair, the mechanisms that drive delamination remain a longstanding open question. Upward motion follows cell shape changes, which are inherently driven by physical forces, but their role is elusive. Here, we investigate delamination in stratifying keratinocytes by combining imaging, force measurements and theoretical modeling. We identify a local change in force balance between differentiating cells and their environment as the key step initiating delamination. Within a homogeneous cell layer with apically polarized contractility, differentiation leads to actomyosin remodeling, redistributing cellular force exertion to the basal side. Such mechanical heterogeneity then results in differentiating cells experiencing and inward basal and outward apical forces that manifest in the formation of a +1 force defect and promote shape changes culminating in upward motion. Simultaneously, delaminating cells actively pull on their underlying neighbors, generating convergent tissue flows which close the basal layer below. Together, we propose a general physical description of delamination initiation, which may act across various multilayered epithelia.
Aga, O.; Moyo, S.; Ferno, J.; Manyahi, J.; Kibwana, U.; Löhr, I.; Langeland, N.; Blomberg, B.; Johnston, I.
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Infections with bacteria which have evolved multi-drug resistance (MDR) cause millions of deaths worldwide. Large-scale efforts are gathering genotypic and phenotypic data on MDR bacteria, but methods for learning the structure, diversity, and predictors of evolutionary pathways to MDR have yet to take full advantage of these data. Here, we use evolutionary accumulation modelling (EvAM), an emerging class of machine learning methods with roots in cancer progression, to infer these evolutionary pathways across ESKAPEE pathogens (seven bacterial species that dominate health burdens), using a database of over 635k genotyped phenotypic observations from around the world. We identify global patterns in MDR evolutionary pathways, remarkably shared across multiple ESKAPEE species. Species-specific deviations from these stereotypical pathways are connected with geographical and demographic covariates, facilitating predictions of future MDR evolution. We verify these predictions with several hundred new phenotypes from ESKAPEE samples spanning decades of clinical infections in sub-Saharan Africa, demonstrating the capacity to forecast future MDR evolution from these inferred shared pathways.