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Gautier, M.

Publications and source records attributed to Gautier, M..

At least 19 recordsLinked to original sources

Isolation and characterization of novel filamentous phages from Swiss-type cheeses infecting the Gram-positive bacterium Propionibacterium freudenreichii

Filamentous phages infecting Gram-positive bacteria remain largely unexplored. Notably, only two filamentous phages, B5 and Philemon infecting Propionibacterium freudenreichii, have been described to date in the phage-rich dairy ecosystem. Although both were genomically characterized, only B5 was confirmed to be an infective filamentous single-stranded DNA phage. The aim of this study was to isolate and characterize new filamentous phages from Swiss-type cheese to investigate their diversity, structural features, host specificity, and potential adaptation to the dairy environment. Thirty raw and pasteurized milk cheeses from France were screened for phages infecting P. freudenreichii strains. Eleven phages were isolated, nine of which displayed a filamentous morphology. Named MINOG1 to MINOG9, these filamentous phages exhibited genomic features typical of this morphotype, including small single-stranded DNA genomes with collinear genes organized into functional modules. Comparison with B5 and Philemon revealed sequence divergence ranging from 0.1% to 7%. These phages also exhibited a diverse host range. To further explore phage-P. freudenreichii interactions, we screened the genomes of the strains used in this study, as well as additional genomes retrieved from the NCBI database, for CRISPR spacers predicted to target these filamentous phages. Numerous strains contained CRISPR spacers showing 79 to 100% identity to genomic regions of these phages. Two P. freudenreichii strains displayed markedly different phage resistance levels despite exact spacer-protospacer matches with phages B5, MINOG1, MINOG2, and MINOG8. Conversely, several strains were resistant to nearly all tested phages despite lacking CRISPR spacers targeting them suggesting the presence of additional defense systems in P. freudenreichii. IMPORTANCEFilamentous phages can play important roles in bacterial ecology by modulating host physiology, population dynamics, and bacterial adaptation to specific environments. However, filamentous phages infecting Gram-positive bacteria remain among the least explored bacterial viruses, and their diversity, ecology, and interactions with their hosts are still poorly understood. This knowledge gap is particularly relevant in dairy ecosystems, where phages are abundant and can influence microbial communities and fermentation processes. In characterizing nine new filamentous phages infecting Propionibacterium freudenreichii from Swiss-type cheeses, this study expands the known diversity of filamentous phages associated with Gram-positive bacteria and provides new insights into phage-host interactions and bacterial defense strategies in dairy-associated bacteria.

microbiology↗

CRY-NLRP3 complexes define a circadian checkpoint controlling inflammasome activation

Innate immune sensors such as the NLRP3 inflammasome can trigger inflammatory responses within minutes, raising the question of how circadian clocks influence such rapid decisions. Here, we identify a protein-level circadian checkpoint that links core clock components to NLRP3 inflammasome activation. We show that NLRP3 associates with the circadian repressors CRY1 and CRY2, forming oscillatory complexes that restrain inflammasome activation and rapidly dissociate upon stimulation. Pharmacological stabilization of CRY proteins preserves CRY-NLRP3 association and attenuates inflammasome assembly, IL-1{beta} secretion and pyroptotic cell death in primary human macrophages. In synchronized macrophages, both NLRP3 inflammasome activation and its inhibition by the NLRP3 inhibitor MCC950 vary with circadian time. Finally, a subset of NLRP3 variants reported in cohorts of patients with Cryopyrin-Associated Periodic Syndromes (CAPS), a group of hereditary fever syndromes caused by mutations in NLRP3, weaken CRY binding and are associated with altered time-of-day patterns of inflammasome activation and MCC950 responsiveness. Together, these findings define CRY-NLRP3 complexes as a circadian checkpoint that modulates inflammasome activity and drug response, revealing time of day as a critical dimension of NLRP3-driven inflammation.

immunology↗

Phenotypic and Genomic Evidence of Adaptive Tracking in Thermal Tolerance of Wild Populations of an Invasive Drosophila.

Adaptive tracking is an evolutionary process in which allele frequencies and phenotypes shift in response to temporally fluctuating environments. Currently it is unclear whether adaptive tracking causes predictable evolution of complex traits such as thermal tolerance. We investigated seasonal adaptive tracking of critical thermal minimum (CTmin) and genome-wide allele frequencies over multiple years in the invasive fly Drosophila suzukii. CTmin increased throughout the growing season, showing a lag of several generations between increasing temperature and evolutionary change. Genetic analyses indicate CTmin is highly polygenic, with little overlap between alleles associated with CTmin and other seasonally fluctuating alleles. Thus, polygenic traits may track seasonal environments without leaving strong genomic signals. By contrast, there were strong seasonal genomic signatures for alleles associated with oligogenic traits as such pesticide resistance and olfactory behavior. These findings suggest that seasonal adaptive tracking shapes a broad suite of traits that contribute to D. suzukiis invasion success.

evolutionary biology↗

Neutrophil terminal programming in the ischemic heart drives fibrosis after myocardial infarction

Following myocardial infarction (MI), the heart undergoes massive neutrophil infiltration characterized by the emergence of distinct subsets, notably a SiglecF+ population that accumulates according to specific temporal dynamics. The mechanisms governing cardiac neutrophil heterogeneity and the subsequent functional impact of this diversity on tissue repair following myocardial infarction remain to be elucidated. Using single-cell RNA-sequencing of neutrophils in the heart and peripheral organs of infarcted mice, we here show that while acquisition of the SiglecF+ state only fully occurs in the ischemic heart tissue, MI primes neutrophils in the periphery to acquire Siglecf and to upregulate receptors for TGF{beta} and GM-CSF that drive acquisition of the SiglecF+ state. Ly6G targeting in vivo shifted cardiac neutrophils towards the SiglecF+ state at day 3 post-MI, induced the emergence of reprogrammed SiglecF+Ly6Glo and Retnlghi neutrophil states at day 5, and was associated with increased fibrosis of the infarct border zone. Mechanistically, Ly6G targeting reshaped the cardiac immune landscape with increased recruitment of pro-fibrotic {gamma}{delta} T cells and monocytes, and SiglecF+ neutrophils exerted direct pro-fibrotic effects on fibroblasts in a co-culture system. Altogether, our results indicate that peripheral neutrophil priming combined with their terminal programming towards a SiglecF+ state in the ischemic heart drives cardiac fibrosis after MI.

physiology↗

The dynamics of barrier locus accumulation during speciation with gene flow

Understanding how reproductive isolation (RI) evolves in the context of gene flow is central to explaining how new species arise. Theory predicts that the accumulation of barrier loci depends on the interplay between divergent selection, recombination, and genomic architecture. However, empirical tests that track these processes across multiple stages of divergence within species remain scarce. The pea aphid complex, which comprises sympatric host-specialised biotypes spanning a continuum of divergence, provides a powerful opportunity to examine how ecological adaptation drives reproductive isolation despite ongoing gene flow. Using whole-genome sequencing data from 13 sympatric European biotypes, we constructed a dense, reference-anchored view of genomic divergence that controls for shared genetic background and recombination landscape. Joint analyses of genetic differentiation, absolute divergence, genetic diversity, recombination, and introgression rates reveal a consistent signature of divergence with gene flow and enable robust identification of barrier loci. Across the divergence continuum, RI is highly polygenic, but barrier loci are clustered and enriched in low-recombination regions and large chromosomal rearrangements, which are expected to strengthen linkage disequilibrium and promote the coupling of barrier effects. While genome-wide differentiation and the number of barrier loci increase gradually with divergence, differentiation within barrier loci displays patterns consistent with non-continuous dynamics, which could reflect threshold effects predicted by theory. Barrier loci contain excesses of salivary effector, detoxification and chemosensory genes, highlighting their central role in host plant specialisation and RI. The representation of these gene categories varies across divergence levels, and some loci are shared among independent biotype comparisons, suggesting common functional routes to specialisation via parallel evolution or introgression. Together, our results provide a comprehensive view of the genomic architecture and evolutionary dynamics underlying speciation with gene flow, illustrating how tightly linked, polygenic architectures can facilitate adaptation and diversification in natural populations.

evolutionary biology↗

A major selective sweep likely linked to insecticide resistance identified along altitudinal gradients in the pine processionary moth

Understanding how natural populations adapt to complex environmental gradients is crucial for predicting evolutionary responses to global change. The pine processionary moth (Thaumetopoea pityocampa), a major forest pest expanding northward and upward in Europe, provides an ideal model to explore genomic adaptation along altitudinal and/or latitudinal gradients. We combined pooled and individual whole- genome resequencing of four pairs of low- and high-elevation populations from Spain, Italy and France (mainland and Corsica) to detect signatures of local adaptation. Population structure analyses revealed strong differentiation among distant populations but limited divergence within altitude pairs. Genome scans identified a few candidate regions under selection, and we notably uncovered a large (~1 Mbp) region showing reduced nucleotide diversity, negative Tajima's D, and fixed allele differences between high- and low-altitude populations, consistent with a recent selective sweep. This region includes a cluster of cytochrome P450 genes and the voltage-gated sodium channel gene para, both involved in detoxification and insecticide resistance. Although signatures of selection were observed at this locus in two distant population pairs, no definitive evidence of recent introgression was found between these distant populations, suggesting independent evolution. Altogether, our results do not show clear evidence for altitudinal adaptation in T. pityocampa, but suggest that xenobiotic exposure could exert a strong selective pressure locally. Our study highlights candidate genes and regions for further investigation of resistance evolution in an insect species in the wild.

evolutionary biology↗

Updating the RZooRoH package for the analysis of inbreeding, identity-by-descent and relatedness from genomic data

The RZooRoH R package was implemented to characterize individual inbreeding levels. It identifies DNA segments inherited twice from a common ancestor through different paths, which are known as homozygous-by-descent (HBD) segments. The package accepts different data formats and provides multiple outputs: HBD segments, inbreeding rates and genome-wide and locus-specific HBD probabilities. In addition, it partitions HBD levels into multiple HBD classes. The length distribution varies between these classes, which therefore correspond to distinct groups of ancestors that can be traced back to different generations in the past. This provides information about mating structure and recent demographic history. The computational performance of the package has been substantially improved, enabling, for example, computing times to be reduced when working with whole-genome sequence data and more HBD classes to be fitted. It is now possible to fit one class per past generation, which facilitates interpretation of the results. Since we have previously demonstrated that the ZooRoH model can be used to characterize identity-by-descent (IBD) between haploid individuals or phased haplotypes, this option has been included in the new package version. Estimating kinship by characterizing IBD levels between the four possible pairs of haplotypes from two individuals is another feature we added to the package. Finally, new options allow models to be refined, for instance by defining HBD classes as intervals or constant inbreeding rates for neighboring classes. Overall, the new version of the package offers improved computational efficiency and interpretability when characterizing inbreeding, IBD and relatedness levels.

genomics↗

Population genomics of incipient allochronic divergence in the Pine Processionary Moth

Allochronic divergence is a key evolutionary mechanism that can frequently lead to incipient speciation. Although theoretical models suggest that such divergence is notably facilitated by small population size and genetic polymorphisms influencing reproductive timing, though constrained by genetic load, empirical validation remains limited. We investigated these predictions by re-analyzing a case of allochronic differentiation between two sympatric populations of pine processionary moth (Thaumetopoea pityocampa) in Portugal, using whole genome resequencing (IndSeq and PoolSeq) of those two populations and eight allopatric ones. We inferred the demographic history of those populations, assessed their genetic load, and searched for genomic regions associated with life cycle differences. Our analyses revealed a recent split between the sympatric allochronic populations, accompanied by a strong reduction in gene flow, bottlenecks, inbreeding, and accumulation of deleterious variants. Genome scans identified several loci associated with life cycle variation, including genes putatively involved in circadian rhythm regulation, predominantly located on the Z chromosome. We discuss how these empirical genomic findings support theoretical expectations that assortative mating driven by differences in reproductive timing, underpinned by polymorphisms in circadian genes, along with genetic drift and purge of genetic load at high-impact sites, can promote the onset and persistence of allochronic divergence.

evolutionary biology↗

A Chromosome-Level Assembly of the Pine Processionary Moth (Thaumetopoea pityocampa) genome

We present a chromosome-level genome assembly and annotation of the pine processionary moth, Thaumetopoea pityocampa (Lepidoptera: Notodontidae), a key forest pest that is a public health concern. The nuclear genome spans 615.9 Mb, scaffolded into 50 chromosome scale and 115 smaller scaffolds, with high completeness (BUSCO score: 98.9%) that provides a decisive improvement over the previous assembly (537 Mb; 68,292 contigs; BUSCO 83.6%). Coverage differences in resequenced males and females allowed identification of the Z chromosome and several W-linked contigs. As ex-pected from previous studies, we found that synteny was largely conserved with related Lepidoptera, although chromosomal fissions may explain the higher chromosome number of 49 autosomes com-pared to typical lepidopteran karyotypes. We also integrated into the assembly linkage map, allowing estimation of a genome-wide male recombination rate of 5.06 cM/Mb, varying from 11.6 cM/Mb to 1.98 cM/Mb from the smallest to the largest chromosomes. Repetitive elements represented 49.1% of this new assembly, dominated by LINEs (45.1% of classified repeats). Finally, gene prediction identified 12,898 gene models, among which 17 circadian rhythm genes were manually curated. Ex-pert annotation further allowed to identify 51 genes of the odorant receptor (OR) family as well as a total of 236 detoxification genes, including 78 CYPs, 56 CCEs, 30 GSTs, 23 UGTs and 49 ABCs. Overall, this assembly represents the first chromosome-level genome for a member of the Thaume-topoeinae subfamily, significantly expanding the currently limited set of genomic resources avail-able for Notodontidae. The fully annotated assembly is publicly accessible through the LepidoDB database (https://bipaa.genouest.org/is/lepidodb/) and will serve as a valuable resource for research on population genomics of this species.

genomics↗

Estimating hierarchical F-statistics from Pool-Seq data

Introduced over seventy years ago, F -statistics have been and remain central to population and evolutionary genetics. Among them, FST is one of the most commonly used descriptive statistics in empirical studies, notably to characterize the structure of genetic polymorphisms within and between populations, to shed light on the evolutionary history of populations, or to identify marker loci under differential selection for adaptive traits. However, the use of FST in simplified population models can overlook important hierarchical structures, such as geographic or temporal subdivisions, potentially leading to misleading interpretations and increasing false positives in genome scans for adaptive differentiation. Hierarchical F -statistics have been introduced to account for multiple predefined levels of population structure. Several estimators have also been proposed, including robust ones implemented in the popular R package hierfstat. Nevertheless, these were primarily designed for individual genotyping data and can be computationally intensive for large genomic datasets. In this study, we extend previous work by developing unbiased method-of-moments estimators for hierarchical F -statistics tailored for Pool-Seq data, a cost-effective alternative to individual genome sequencing. These Pool-Seq estimators have been developed in an anova framework, using definitions based on identity-in-state probabilities. The new estimators have been implemented in an updated version of the R package poolfstat, together with estimators for sample allele count data derived from individual genotyping data. We validate and compare the performance of these estimators through extensive simulations under a hierarchical island model. Finally, we apply these estimators to real Pool-Seq data from Drosophila melanogaster populations, demonstrating their usefulness in revealing population structure and identifying loci with high differentiation within or between groups of subpopulations and associated with spatial or temporal genetic variation.

genetics↗

Footprints of worldwide adaptation in structured populations of D. melanogaster through the expanded DEST 2.0 genomic resource

Large scale genomic resources can place genetic variation into an ecologically informed context. To advance our understanding of the population genetics of the fruit fly Drosophila melanogaster, we present an expanded release of the community-generated population genomics resource Drosophila Evolution over Space and Time (DEST 2.0; https://dest.bio/). This release includes 530 high-quality pooled libraries from flies collected across six continents over more than a decade (2009-2021), most at multiple time points per year; 211 of these libraries are sequenced and shared here for the first time. We used this enhanced resource to elucidate several aspects of the species demographic history and identify novel signs of adaptation across spatial and temporal dimensions. We showed that patterns of secondary contact, originally characterized in North America, are replicated in South America and Australia. We also found that the spatial genetic structure of populations is stable over time, but that drift due to seasonal contractions of population size causes populations to diverge over time. We identified signals of adaptation that vary between continents in genomic regions associated with xenobiotic resistance, consistent with independent adaptation to common pesticides. Moreover, by analyzing samples collected during spring and fall across Europe, we provide new evidence for seasonal adaptation related to loci associated with pathogen response. Furthermore, we have also released an updated version of the DEST genome browser. This is a useful tool for studying spatio-temporal patterns of genetic variation in this classic model system.

evolutionary biology↗

New insights into past and future invasion of Drosophila suzukii using novel genomic resources and statistical methods to combine individual and pool sequencing data

Global change is accelerating biological invasions, making it crucial to understand how species adapt in new environments to improve management strategies. Genomic data provide valuable insights into adaptation through Genotype-Environment Association (GEA) studies, which identify genes and biological processes tied to invasion success, and through geometric Genomic Offset (gGO) statistics, which estimate genetic (mal)adaptation to new environments. Here, we investigate genetic adaptation in the invasive pest Drosophila suzukii using novel genomic resources and statistical methods. We use a new chromosome-level genome assembly and data from 37 populations, combining publicly available and newly generated pooled and individual sequencing data, analyzed with an enhanced version of BayPass software, tailored for such hybrid datasets. First, we identify genomic regions showing genetic differentiation between native and invasive populations. Then, using a GEA with 29 environmental covariates, we estimate the gGO between the source environments and the invaded areas, shedding light on the potential adaptive challenges D. suzukii faced during previous invasions. In addition, we estimate gGO for geographical areas not yet invaded to predict future invasion risks, and identify regions from which preadapted populations may originate. Our results reveal numerous genomic regions associated with the invasive status from genome scans. However, when considering broader patterns of adaptation to specific environmental variables through gGO analyses, we find that D. suzukii populations likely faced only limited adaptive challenges across their major invasion range, while certain uninvaded regions still remain at high risk of future invasion. Our study offers significant insights into D. suzukii adaptation and provides a practical population genomics framework to predict biological invasions, applicable to various species.

evolutionary biology↗

Transposable element accumulation drives genome size increase in Hylesia metabus (Lepidoptera: Saturniidae), an urticating moth species from South America

We present the first nuclear genome assembly and a complete mitogenome for Hylesia metabus (Arthropoda; Insecta; Lepidoptera; Saturniidae). The assembled nuclear genome sequence is 1,271 Mb long, which is among the 10 largest lepidopteran genome assemblies published to date. It is scaffolded in 31 pseudo chromosomes, has a BUSCO score of 99.5%, and has a highly conserved synteny compared to phylogenetically close species. Repetitive elements make up 67% of the nuclear genome and are mainly located in intergenic regions, among which LINEs were predominant, with CR1-Zenon being the most abundant. Phylogenetic and comparative analyses of H. metabus assembly and 17 additional Saturniidae and Sphingidae assemblies suggested that an accumulation of repetitive elements likely led to the increased size of H. metabus genome. Gene annotation using Helixer identified 26,122 transcripts. The Z scaffold was identified using both a synteny analysis and variations of coverage for two resequenced male and female H. metabus. The H. metabus nuclear genome and mitogenome assemblies can be found and browsed on the BIPAA website and constitute useful resources for future population and comparative genomics studies.

genomics↗

Identification of perturbation-responsive regions and genes in comparative spatial transcriptomics atlases

We introduce Vespucci, a machine-learning method to identify perturbation-responsive regions, genes and gene programs within comparative spatial transcriptomics atlases. We validate Vespucci on simulated and published datasets and show that it outperforms 19 published computational methods for spatial transcriptomics. We apply Vespucci to expose the spatial organization of gene programs activated by therapies that guide repair of the injured spinal cord.

bioinformatics↗

Genomic prediction of individual inbreeding levels for the management of genetic diversity in populations with small effective size

In populations of small effective size (Ne), such as those in conservation programs, companion animals or livestock species, management of diversity and inbreeding is essential. Homozygosity-by-descent (HBD) segments provide relevant information in that context, as they allow efficient estimation of the inbreeding coefficient, provide locus-specific information and their length is informative about the "age" of inbreeding. Therefore, our objective was to evaluate tools for predicting HBD in future offspring based on parental genotypes, a problem equivalent to identifying segments identical-by-descent (IBD) among the four parental chromosomes. In total, we reviewed and evaluated 16 approaches using simulated and real data with small Ne. The methods included model-based approaches, mostly hidden Markov models (HMMs), which considered up to 15 IBD configurations among the four parental chromosomes, as well as more computationally efficient rule-based approaches. The accuracy of the methods was then evaluated, including with low-density marker panels, genotyping-by-sequencing data and small groups of individuals, typical features in such populations. Two HMMs performed consistently well, while two rule-based approaches proved efficient for genome-wide predictions. The model-based approaches were particularly efficient when information was reduced (low marker density, locus-specific estimation). Methods using phased data proved to be more efficient, while some approaches relying on unphased genotype data proved to be sensitive to the allele frequencies used. In some settings, pedigree information was competitive in predicting recent inbreeding levels. Finally, we showed that our evaluation is also informative about the accuracy of the methods for estimating relatedness and identifying IBD segments between pairs of individuals.

genomics↗

THE NEURONAL ARCHITECTURE OF AUTONOMIC DYSREFLEXIA

Autonomic dysreflexia is a life-threatening medical condition characterized by episodes of uncontrolled hypertension that occur in response to sensory stimuli after spinal cord injury (SCI)1-7. The fragmented understanding of the mechanisms underlying autonomic dysreflexia hampers the development of therapeutic strategies to manage this condition, leaving people with SCI at daily risk of heart attack and stroke8-18. Here, we expose the complete de novo neuronal architecture that develops after SCI and causes autonomic dysreflexia. In parallel, we uncover a competing, yet overlapping neuronal architecture activated by epidural electrical stimulation of the spinal cord that safely regulates blood pressure after SCI. The discovery that these adversarial neuronal architectures converge onto a single neuronal subpopulation provided a blueprint for the design of a mechanism-based intervention that reversed autonomic dysreflexia in mice, rats, and humans with SCI. These results establish a path for the effective treatment of autonomic dysreflexia in people with SCI.

neuroscience↗

Predicting species invasiveness with genomic data: is Genomic Offset related to establishment probability?

Predicting the risk of establishment and spread of populations outside their native range represents a major challenge in evolutionary biology. Various methods have recently been developed to estimate population (mal)adaptation to a new environment with genomic data via so-called Genomic Offset (GO) statistics. These approaches are particularly promising for studying invasive species, but have still rarely been used in this context. Here, we evaluated the relationship between GO and the estab-lishment probability of a population in a new environment using both in silico and empirical data. First, we designed invasion simulations to evaluate the ability to predict establishment probability of two GO computation methods (Geometric GO and Gradient Forest) under several conditions. Additionally, we aimed to evaluate the interpretability of absolute Geometric GO values, which the-oretically represent the adaptive genetic distance between populations from distinct environments. Second, utilizing public real data from the crop pest species Bactrocera tryoni, a fruit fly native from Northern Australia, we computed GO between "source" populations and a diverse range of locations within invaded areas. This practical application of GO within the context of a biological invasion underscores its potential in providing insights and guiding recommendations for future invasion risk assessment. Overall, our results suggest that GO statistics represent good predictors of the estab-lishment probability and may thus inform invasion risk, although the influence of several factors on prediction performance (e.g. propagule pressure or admixture) will need further investigation.

evolutionary biology↗

Genomic reconstruction of the successful establishment of a feralized bovine population on the subantarctic island of Amsterdam

The feral cattle of the subantarctic island of Amsterdam provide an outstanding case study of a large mammalian population that was established by a handful of founders and thrived within a few generations in a seemingly inhospitable environment. Here, we investigated the genetic history and composition of this population using genotyping and sequencing data. Our inference showed an intense but brief founding bottleneck around the late 19th century and revealed contributions from European taurine and Indian Ocean zebu in the founder ancestry. Comparative analysis of whole genome sequences further revealed a moderate reduction in genetic diversity despite high levels of inbreeding. The brief and intense bottleneck was associated with high levels of drift, a flattening of the site frequency spectrum and a slight relaxation of purifying selection on mildly deleterious variants. However, we did not observe any significant purge of highly deleterious variants. Interestingly, the populations success in the harsh environment can be attributed to pre-adaptation from their European taurine ancestry, suggesting no strong bioclimatic challenge, and also contradicting evidence for insular dwarfism. Genome scan for footprints of selection uncovered a majority of candidate genes related to nervous system function, likely reflecting rapid feralization driven by behavioral changes and complex social restructuring. This unprecedented case study provides valuable insights into rapid population establishment, feralization, and genetic adaptation in challenging environments. It highlights the importance of preserving the unique genetic legacies of feral populations and raises ethical questions in the eyes of conservation efforts.

evolutionary biology↗