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PubMed2004

Phages and the evolution of bacterial pathogens: from genomic rearrangements to lysogenic conversion.

Comparative genomics demonstrated that the chromosomes from bacteria and their viruses (bacteriophages) are coevolving. This process is most evident for bacterial pathogens where the majority contain prophages or phage remnants integrated into the bacterial DNA. Many prophages from bacterial pathogens encode virulence factors. Two situations can be distinguished: Vibrio cholerae, Shiga toxin-producing Escherichia coli, Corynebacterium diphtheriae, and Clostridium botulinum depend on a specific prophage-encoded toxin for causing a specific disease, whereas Staphylococcus aureus, Streptococcus pyogenes, and Salmonella enterica serovar Typhimurium harbor a multitude of prophages and each phage-encoded virulence or fitness factor makes an incremental contribution to the fitness of the lysogen. These prophages behave like "swarms" of related prophages. Prophage diversification seems to be fueled by the frequent transfer of phage material by recombination with superinfecting phages, resident prophages, or occasional acquisition of other mobile DNA elements or bacterial chromosomal genes. Prophages also contribute to the diversification of the bacterial genome architecture. In many cases, they actually represent a large fraction of the strain-specific DNA sequences. In addition, they can serve as anchoring points for genome inversions. The current review presents the available genomics and biological data on prophages from bacterial pathogens in an evolutionary framework.

Bacteria↗
PubMed2026

Large-scale genomic analysis places Chinese CC398 as a persistent human-associated MSSA lineage apart from the dominant global LA-MRSA clade.

Staphylococcus aureus clonal complex (CC)398 has emerged as a dominant livestock-associated methicillin-resistant S. aureus (LA-MRSA) lineage worldwide; however, its evolutionary trajectory and regional diversification remain incompletely understood. We developed a core-genome multilocus sequence typing (cgMLST) scheme with hierarchical clustering and applied it to over 30,000 S. aureus genomes, revealing frequent cross-border transmission of CC398. Subsequent time-calibrated phylogenetic analysis placed the most recent common ancestor at 1942 (95% CI: 1939-1945), with the human-to-livestock host jump around 1969 (95% CI: 1968-1972). Chinese CC398 exhibits a distinct trajectory: unlike the LA-MRSA lineages dominating Europe and North America, Chinese isolates are predominantly human-associated methicillin-susceptible S. aureus (HA-MSSA), forming unique East Asia-specific phylogroups (SAP1, SAP2, and AP1-AP3), with distinct resistance and virulence profiles. The LA lineage remains limited in China, with multinational mixed clusters emerging only after 2019. Analysis of global transmission networks revealed a significant correlation between LA-CC398 spread and international trade in fresh swine products, while no such correlation was observed for the human-associated lineage. Beyond the established lineage markers tet(M) and scn, our analysis identified additional differentially distributed genes, including cadC-a chromosomal cadmium resistance regulator-as a novel HA-lineage-enriched gene whose functional role in host adaptation remains to be determined. This study reveals that CC398 followed fundamentally different evolutionary paths in China versus Western countries, challenging a one-size-fits-all model of its dissemination.IMPORTANCEThis study illustrates how large-scale microbial genomics can resolve the evolutionary origins and regional diversification of bacterial pathogens. By applying a novel cgMLST scheme to over 30,000 S. aureus genomes, we show that CC398 followed fundamentally different evolutionary paths in China versus Western countries-challenging the prevailing model of uniform global dissemination-and that livestock-associated MRSA expansion is closely linked to international trade in fresh pork products. These findings highlight the need for integrated surveillance across human, animal, and trade interfaces to anticipate the emergence and spread of zoonotic pathogens.

Staphylococcus aureus↗
PubMed1995

Association of orogenic activity with the Ordovician radiation of marine life.

The Ordovician radiation of marine life was among the most substantial pulses of diversification in Earth history and coincided in time with a major increase in the global level of orogenic activity. To investigate a possible causal link between these two patterns, the geographic distributions of 6576 individual appearances of Ordovician vician genera around the world were evaluated with respect to their proximity to probable centers of orogeny (foreland basins). Results indicate that these genera, which belonged to an array of higher taxa that diversified in the Middle and Late Ordovician (trilobites, brachiopods, bivalves, gastropods, monoplacophorans), were far more diverse in, and adjacent to, foreland basins than they were in areas farther removed from orogenic activity (carbonate platforms). This suggests an association of orogeny with diversification at that time.

Biological Evolution↗
PubMed2005

Thysanoptera: diversity and interactions.

Published literature on thrips has been dominated by descriptive taxonomy, pest control work, and generalized synecology. The lack of studies examining the detailed biology or autecology of any species limits our understanding of how thrips live and the processes underlying their diversification. Similarly, the phylogenetic inadequacy of thrips classification limits our ability to examine the evolution of biological traits. The extent to which our knowledge of the biology of thrips has increased in recent years is reviewed, such as the behavior of particular species and their interactions with other organisms, including host plant associations, pollination, predation, and natural enemies--factors involved in driving diversification within this order of opportunistic insects.

Animals↗
PubMed1999

Evolution of antigen binding receptors.

This review addresses issues related to the evolution of the complex multigene families of antigen binding receptors that function in adaptive immunity. Advances in molecular genetic technology now permit the study of immunoglobulin (Ig) and T cell receptor (TCR) genes in many species that are not commonly studied yet represent critical branch points in vertebrate phylogeny. Both Ig and TCR genes have been defined in most of the major lineages of jawed vertebrates, including the cartilaginous fishes, which represent the most phylogenetically divergent jawed vertebrate group relative to the mammals. Ig genes in cartilaginous fish are encoded by multiple individual loci that each contain rearranging segmental elements and constant regions. In some loci, segmental elements are joined in the germline, i.e. they do not undergo genetic rearrangement. Other major differences in Ig gene organization and the mechanisms of somatic diversification have occurred throughout vertebrate evolution. However, relating these changes to adaptive immune function in lower vertebrates is challenging. TCR genes exhibit greater sequence diversity in individual segmental elements than is found in Ig genes but have undergone fewer changes in gene organization, isotype diversity, and mechanisms of diversification. As of yet, homologous forms of antigen binding receptors have not been identified in jawless vertebrates; however, acquisition of large amounts of structural data for the antigen binding receptors that are found in a variety of jawed vertebrates has defined shared characteristics that provide unique insight into the distant origins of the rearranging gene systems and their relationships to both adaptive and innate recognition processes.

Amphibians↗
PubMed1986

Hybridization approaches to the study of neuropeptides.

During the course of evolution, species have increased in complexity, and their nervous systems have evolved correspondingly with an increase in the diversity of their capabilities to respond. Part of that diversity has resulted from an increase in cell types and numbers and their interconnections. In addition, much of it comes from the panoply of neurotransmitters available, of which the neuropeptides represent a major portion. The application of the techniques of molecular biology to the nervous system has led to an appreciation of some of the genetic means by which such diversity can be generated. The cloning and sequencing of peptide precursor genes has shown the existence of gene families, genes with duplications of internal sequences, and genes evolutionarily related to one another, suggesting that one response to the increasing complexity of the organism has been a genetic diversification of the precursor population for peptides. As the precursor genes evolved and thereby provided increasing numbers of peptides, the receptor genes may have evolved simultaneously to provide diversification in the responses to these peptides (for example, the opioid peptide precursors) (Comb et al 1983). The precursor sequences obtained have led not only to the predictions of new peptides but also to the discovery of alternative methods of generating diversity from a single gene. At one extreme, the gene is translated into a polyprotein containing several peptides, which are produced in and released from the same cell. At the other extreme, the nuclear transcript of the gene is differentially spliced such that one peptide is expressed in one tissue and another in a different tissue (Calcitonin-CGRP), or one peptide may be expressed with or without a second peptide in different cells (substance P-substance K). The net result is either one neuron producing a multiplicity of responses to several co-released peptides derived from a polyprotein (POMC or PE) or a tissue- or cell-specificity in terms of which peptide is produced and released. Numerous applications have been made utilizing the cDNA probes generated from the cloning of neuropeptide precursors. Hybridization analyses, including in vitro transcription run-off, have demonstrated that the transcription of neuropeptide genes is regulated by transsynaptic activation of transmitter receptors located in the neuronal membrane, or by hormones, or by as yet unveiled mechanisms. Hybridization techniques have allowed assessment of the dynamic state of neuropeptides functioning as neuromodulators.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenal Medulla↗
PubMed2006

Switching on chromosomal translocations.

Activation-induced deaminase initiates three different antibody diversification reactions: class switch recombination, somatic hypermutation (SHM), and gene conversion. We have shown that, in addition to antibody diversification, activation-induced deaminase can also initiate Burkitt's lymphoma-like c-myc/IgH translocations. However, distinct DNA damage- and oncogene-induced checkpoints operate in B cells to produce a normal intrachromosomal class switch recombination event or an aberrant interchromosomal fusion. These findings open the way to study the molecular pathways taking place at the early stages of malignant transformation.

Cell Transformation, Neoplastic↗
PubMed2026

Reversing-or Rewiring-Lineage Plasticity? Lessons from EZH2 Loss in Prostate Cancer.

Enhancer of zeste homolog 2 (EZH2) inhibitors have been proposed to counteract lineage plasticity (LP) in prostate cancer and thereby resensitize tumors to androgen receptor (AR) inhibition. In this issue of Cancer Research, Jacobi and colleagues provide new mechanistic insights into EZH2 biology across prostate cancer progression using a genetically engineered mouse model that recapitulates the transition toward a neuroendocrine (NE) phenotype. Unexpectedly, genetic deletion of Ezh2 did not reverse LP but instead promoted the diversification of transcription factor (TF) programs driving NE differentiation. In particular, the loss of EZH2 activated members of the KLF TF family, which contributed to this transcriptional diversification. Moreover, EZH2 deletion altered the chromatin-binding landscape of AR, redirecting it toward KLF-associated genomic sites. Collectively, these results refine our understanding of EZH2 function in prostate cancer: Rather than simply reversing LP, EZH2 loss rewires transcriptional networks and reshapes the AR cistrome. These findings are timely given the growing number of clinical trials testing EZH2 inhibitors in metastatic prostate cancer and highlight the need to define when and how to deploy EZH2 inhibition to exploit its effects on tumor lineage dynamics. See related article by Jacobi et al., p. 889.

Male↗
PubMed2026

Spatial Integration of Protein and Chromosomal States Reveals Early Copy-Number Changes and Genotype-Associated Immune Neighborhoods in Serous Ovarian Cancer Evolution.

UNLABELLED: Detecting chromosomal copy-number alterations together with protein-defined cell states in intact tissue is critical for understanding early clonal evolution and microenvironmental interactions in cancer. We developed ORION-FISH, which integrates high-plex tissue imaging with a morphology-preserving DNA fluorescence in situ hybridization (DNA-FISH) workflow and single-cell registration, yielding measurements concordant with clinical FISH. In high-grade serous ovarian carcinoma (HGSOC), ORION-FISH recapitulated known chromosomal changes while revealing subclonal heterogeneity missed by targeted sequencing. Applied to serous tubal intraepithelial carcinomas, precursors of HGSOC, ORION-FISH identified intermixed epithelial cells with MYC or CCNE1 copy-number gains, as well as concurrent alterations associated with distinct immune microenvironments. In addition, epithelial cells with MYC and CCNE1 copy-number gains were detected in morphologically normal fallopian tube epithelium, along with rare MDM4 increases across epithelial lineages. Together, ORION-FISH provides a framework linking chromosomal copy-number states to protein-defined phenotypes within preserved tissue architecture, enabling context-aware interrogation of early copy-number diversification at single-cell resolution. SIGNIFICANCE: We introduce ORION-FISH, a spatially resolved workflow integrating multiplexed protein imaging with DNA-FISH to map genomic alterations within intact tissues. Applying this approach to ovarian cancer precursors reveals early copy-number diversification and associations with the local immune context, providing a foundation for studying how genomic and microenvironmental states coevolve during tumor initiation.

Female↗
PubMed2004

Keeping sensory cells and evolving neurons to connect them to the brain: molecular conservation and novelties in vertebrate ear development.

The evolution of the mechanosensory cellular module and the molecular details that regulate its development has included morphological modifications of these cells as well as the formation of larger assemblies of mechanosensory cell aggregates among metazoans. This has resulted in a wide diversity of mechanosensory organs. The wide morphological diversity of organs, including the associated morphological modifications of the mechanosensory cells, suggests parallel evolution of these modules and their associated organs. This morphological diversity is in stark contrast to the molecular conservation of developmental modules across phyla. These molecular data suggest that the evolution of mechanosensory transduction might have preceded that of distinct cellular differentiation. However, once a molecular network governing development of specialized cells involved in mechanosensory transduction evolved, that molecular network was preserved across phyla. Present data suggest that at least the common ancestor of triploblastic organisms, perhaps even the common diploblastic ancestor of bilaterian metazoans, had molecular and cellular specializations for mechanosensation. It is argued that the evolution of multicellular organs dedicated to specific aspects of mechanosensation, such as gravity and sound perception, are evolutionary transformations that build on this conserved molecular network for cellular specialization, but reflect distinct morphological solutions. We propose that the sensory neurons, connecting the craniate ear with the brain, are a derived feature of craniates, and possibly chordates, that came about through diversification of the lineage forming mechanosensory cells during development. This evolutionarily late event suggests a heterochronic shift, so that sensory neurons develop in mammals prior to mechanosensory hair cells. However, sensory neuron development is connected to hair cell development, likely in a clonal relationship. The theme of cellular conservation is reiterated in two examples of chordate otic diversification: the evolution of the horizontal canal system and the evolution of the basilar papilla/cochlea. It is suggested that here again, cellular multiplication and formation of a special epithelium predates the functional transformation to an 'organ' system for horizontal angular acceleration and sound pressure reception, respectively. Overall, evolution of the vertebrate ear needs to be understood as an interplay between and utilization of two gene networks or modules. One is at the level of the molecularly and developmentally conserved mechanosensory cellular module. The other is an increased complexity in the morphology of both adult mechanosensory cells and organs by the addition of end-stage and novel features and associated gene networks to detect specific aspects of mechanosensory stimuli.

Animals↗
PubMed2005

Evolutionary patterns of cranial nerve efferent nuclei in vertebrates.

All vertebrates have a similar series of rhombomeric hindbrain segments within which cranial nerve efferent nuclei are distributed in a similar rostrocaudal sequence. The registration between these two morphological patterns is reviewed here to highlight the conserved vs. variable aspects of hindbrain organization contributing to diversification of efferent sub-nuclei. Recent studies of segmental origins and migrations of branchiomotor, visceromotor and octavolateral efferent neurons revealed more segmental similarities than differences among vertebrates. Nonetheless, discrete variations exist in the origins of trigeminal, abducens and glossopharyngeal efferent nuclei. Segmental variation of the abducens nucleus remains the sole example of efferent neuronal homeosis during vertebrate hindbrain evolution. Comparison of cranial efferent segmental variations with surrounding intrinsic neurons will distinguish evolutionary changes in segment identity from lesser transformations in expression of unique neuronal types. The diversification of motoneuronal subgroups serving new muscles and functions appears to occur primarily by elaboration within and migration from already established segmental efferent pools rather than by de novo specification in different segmental locations. Identifying subtle variations in segment-specific neuronal phenotypes requires studies of cranial efferent organization within highly diverse groups such as teleosts and mammals.

Animals↗
PubMed1988

Variation in neuromuscular activity during prey capture by trophic specialists and generalists (Pisces: Labridae).

Members of the marine teleost family Labridae are among the most abundant and morphologically diverse fish on coral reefs. A quantitative analysis was conducted of the neuromuscular activity patterns controlling movement of the jaws during prey capture by 4 labrid species ranging from trophic specialists to trophic generalists. A total of more than 800 captures of 3 prey types was analyzed. All 4 species showed significant modulation of electromyographic parameters in response to different prey types. Significant variation was also found between replicate experiments on the same individuals. To obtain valid assessments of interspecific variability, statistical analyses must take into account this potentially high degree of intraspecific variability. By partitioning the variance in a nested analysis of variance, a lack of significant differences in electromyographic parameters between species became apparent. In contrast to the closely related Cichlidae, trophic diversification in the Labridae has not been accompanied by the acquisition of unique neuromuscular activity patterns for prey capture. The dramatic adaptive radiation that has occurred in these 2 families has involved different processes of evolutionary diversification. Neuromuscular stereotypy of labrids may be associated with the lack of structural flexibility in their 'coupled jaw'. Additional study is needed to establish the extent to which labrid radiation into various trophic niches is related to the evolution of specialized morphologies and foraging behaviors.

Animals↗
PubMed2004

Bifurcation into functional niches in adaptation.

One of the central questions in evolutionary biology concerns the dynamics of adaptation and diversification. This issue can be addressed experimentally if replicate populations adapting to identical environments can be investigated in detail. We have studied 501 such replicas using digital organisms adapting to at least two fundamentally different functional niches (survival strategies) present in the same environment: one in which fast replication is the way to live, and another where exploitation of the environment's complexity leads to complex organisms with longer life spans and smaller replication rates. While these two modes of survival are closely analogous to those expected to emerge in so-called r and K selection scenarios respectively, the bifurcation of evolutionary histories according to these functional niches occurs in identical environments, under identical selective pressures. We find that the branching occurs early, and leads to drastic phenotypic differences (in fitness, sequence length, and gestation time) that are permanent and irreversible. This study confirms an earlier experimental effort using microorganisms, in that diversification can be understood at least in part in terms of bifurcations on saddle points leading to peak shifts, as in the picture drawn by Sewall Wright.

Adaptation, Biological↗
PubMed1992

Project risk definition and measurement in a not-for-profit setting.

The health care finance literature on capital investment decisions generally applies conventional market risk concepts without distinguishing between proprietary and not-for-profit forms of organization. Since proprietary firms have shareholder wealth maximization as their primary goal, a project's relevant risk is its contribution to the riskiness of the equity investors' well diversified stock portfolios, or its market risk. However, not-for-profit organizations do not have shareholder wealth maximization as their primary goal, and thus market risk concepts are not applicable. Rather, the relevant risk in a not-for-profit setting is a project's corporate risk; that is, the project's contribution to the riskiness of the organization. The difference in risk definition and measurement between proprietary and not-for-profit firms has two implications for managerial decisions: (1) in making capital investment decisions, a manager must define and measure a project's riskiness on the basis of the firm's organizational form; and (2) although diversification for the sole purpose of risk reduction is not a valid rationale for proprietary firms because stockholders can achieve the same result at less cost, risk-reducing diversification does make sense for not-for-profit firms.

Capital Expenditures↗
PubMed1997

Salivary glands: a paradigm for diversity of gland development.

The major salivary glands of mammals are represented by three pairs of organs that cooperate functionally to produce saliva for the oral cavity. While each type of gland produces a signature secretion that complements the secretions from the other glands, there is also redundancy as evidenced by secretion of functionally similar and, in some cases, identical products in the three glands. This, along with their common late initiation of development, in fetal terms, their similarities in developmental pattern, and their proximate sites of origin, suggests that a common regulatory cascade may have been shared until shortly before the onset of overt gland development. Furthermore, occasional ectopic differentiation of individual mature secretory cells in the "wrong" gland suggests that control mechanisms responsible for the distinctive cellular composition of each gland also share many common steps, with only minor differences providing the impetus for diversification. To begin to address this area, we examine here the origins of the salivary glands by reviewing the expression patterns of several genes with known morphogenetic potential that may be involved based on developmental timing and location. The possibility that factors leading to determination of the sites of mammalian salivary gland development might be homologous to the regulatory cascade leading to salivary gland formation in Drosophila is also evaluated. In a subsequent section, cellular phenotypes of neonatal and adult glands are compared and evaluated for insights into the mechanisms and lineages leading to cellular diversification. Finally, the phenomena of proliferation, repair, and regeneration in adult salivary glands are reviewed, with emphasis on the extent to which the cellular diversity is reversible and which cell type other than stem cells has the ability to redifferentiate into other cell types.

Animals↗
PubMed2006

Evolution of the P-type II ATPase gene family in the fungi and presence of structural genomic changes among isolates of Glomus intraradices.

BACKGROUND: The P-type II ATPase gene family encodes proteins with an important role in adaptation of the cell to variation in external K+, Ca2+ and Na2+ concentrations. The presence of P-type II gene subfamilies that are specific for certain kingdoms has been reported but was sometimes contradicted by discovery of previously unknown homologous sequences in newly sequenced genomes. Members of this gene family have been sampled in all of the fungal phyla except the arbuscular mycorrhizal fungi (AMF; phylum Glomeromycota), which are known to play a key-role in terrestrial ecosystems and to be genetically highly variable within populations. Here we used highly degenerate primers on AMF genomic DNA to increase the sampling of fungal P-Type II ATPases and to test previous predictions about their evolution. In parallel, homologous sequences of the P-type II ATPases have been used to determine the nature and amount of polymorphism that is present at these loci among isolates of Glomus intraradices harvested from the same field. RESULTS: In this study, four P-type II ATPase sub-families have been isolated from three AMF species. We show that, contrary to previous predictions, P-type IIC ATPases are present in all basal fungal taxa. Additionally, P-Type IIE ATPases should no longer be considered as exclusive to the Ascomycota and the Basidiomycota, since we also demonstrate their presence in the Zygomycota. Finally, a comparison of homologous sequences encoding P-type IID ATPases showed unexpectedly that indel mutations among coding regions, as well as specific gene duplications occur among AMF individuals within the same field. CONCLUSION: On the basis of these results we suggest that the diversification of P-Type IIC and E ATPases followed the diversification of the extant fungal phyla with independent events of gene gains and losses. Consistent with recent findings on the human genome, but at a much smaller geographic scale, we provided evidence that structural genomic changes, such as exonic indel mutations and gene duplications are less rare than previously thought and that these also occur within fungal populations.

Base Sequence↗
PubMed2006

A survey of nuclear ribosomal internal transcribed spacer substitution rates across angiosperms: an approximate molecular clock with life history effects.

BACKGROUND: A full understanding of the patterns and processes of biological diversification requires the dating of evolutionary events, yet the fossil record is inadequate for most lineages under study. Alternatively, a molecular clock approach, in which DNA or amino acid substitution rates are calibrated with fossils or geological/climatic events, can provide indirect estimates of clade ages and diversification rates. The utility of this approach depends on the rate constancy of molecular evolution at a genetic locus across time and across lineages. Although the nuclear ribosomal internal transcribed spacer region (nrITS) is increasingly being used to infer clade ages in plants, little is known about the sources or magnitude of variation in its substitution rate. Here, we systematically review the literature to assess substitution rate variation in nrITS among angiosperms, and we evaluate possible correlates of the variation. RESULTS: We summarize 28 independently calibrated nrITS substitution rates ranging from 0.38 x 10(-9) to 8.34 x 10(-9) substitutions/site/yr. We find that herbaceous lineages have substitution rates almost twice as high as woody plants, on average. We do not find any among-lineage phylogenetic constraint to the rates, or any effect of the type of calibration used. Within life history categories, both the magnitude of the rates and the variance among rates tend to decrease with calibration age. CONCLUSION: Angiosperm nrITS substitution rates vary by approximately an order of magnitude, and some of this variation can be attributed to life history categories. We make cautious recommendations for the use of nrITS as an approximate plant molecular clock, including an outline of more appropriate phylogenetic methodology and caveats against over interpretation of results. We also suggest that for lineages with independent calibrations, much of the variation in nrITS substitution rates may come from uncertainty in calibration date estimates, highlighting the importance of accurate and/or multiple calibration dates.

Amino Acid Substitution↗
PubMed2006

Tracking the connection between evolutionary and functional shifts using the fungal lipase/feruloyl esterase A family.

BACKGROUND: There have been many claims of adaptive molecular evolution, but what role does positive selection play in functional divergence? The aim of this study was to test the relationship between evolutionary and functional shifts with special emphasis on the role of the environment. For this purpose, we studied the fungal lipase/feruloyl esterase A family, whose functional diversification makes it a very promising candidate. RESULTS: The results suggested functional shift following a duplication event where neofunctionalisation of feruloyl esterase A had occurred with conservation of the ancestral lipase function. Evolutionary shift was detected using the branch-site model for testing positive selection on individual codons along specific lineages. Positively selected amino acids were detected. Furthermore, biological data obtained from site-directed mutagenesis experiments clearly demonstrated that certain amino acids under positive selection were involved in the functional shift. We reassessed evolutionary history in terms of environmental response, and hypothesized that environmental changes such as colonisation by terrestrial plants might have driven adaptation by functional diversification in Euascomycetes (Aspergilli), thus conferring a selective advantage on this group. CONCLUSION: The results reported here illustrate a rare example of connection between fundamental events in molecular evolution. We demonstrated an unequivocal connection between evolutionary and functional shifts, which led us to conclude that these events were probably linked to environmental change.

Amino Acids↗