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Results for “phenotypic plasticity”

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At least 19 recordsLinked to original sources

PubMed2024

Environmental epigenetics: Exploring phenotypic plasticity and transgenerational adaptation in fish.

Epigenetics plays a vital role in the interaction between living organisms and their environment by regulating biological functions and phenotypic plasticity. Considering that most aquaculture activities take place in open or natural habitats that are vulnerable to environmental changes. Promising findings from recent research conducted on various aquaculture species have provided preliminary evidence suggesting a link between epigenetic mechanisms and economically valuable characteristics. Environmental stressors, including climate changes (thermal stress, hypoxia, and water salinity), anthropogenic impacts such as (pesticides, crude oil pollution, nutritional impacts, and heavy metal) and abiotic factors (infectious diseases), can directly trigger epigenetic modifications in fish. While experiments have confirmed that many epigenetic alterations caused by environmental factors have plastic responses, some can be permanently integrated into the genome through genetic integration and promoting rapid transgenerational adaptation in fish. These environmental factors might cause irregular DNA methylation patterns in genes related to many biological events leading to organs dysfunction by inducing alterations in genes related to oxidative stress or apoptosis. Moreover, these environmental issues alter DNA/histone methylation leading to decreased reproductive competence. This review emphasizes the importance of understanding the effects of environmentally relevant issues on the epigenetic regulation of phenotypic variations in fish. The goal is to expand our knowledge of how epigenetics can either facilitate or hinder species' adaptation to these adverse conditions. Furthermore, this review outlines the areas that warrant further investigation in understanding epigenetic reactions to various environmental issues.

Animals↗

PubMed1992

Phenotypic plasticity of avian embryonic sympathetic neurons grown in a chemically defined medium: direct evidence for noradrenergic and cholinergic properties in the same neurons.

Avian embryonic sympathetic ganglia possess both catecholaminergic and cholinergic features and can synthesize noradrenaline (NAd) and acetylcholine (ACh) simultaneously. In the present study we sought to determine (1) whether or not this coproduction of NAd and ACh corresponds to the existence of two non-overlapping populations, and (2) to what extent the levels of synthesis are influenced by non-neuronal ganglion cells. We have focused on the correlation between the immunocytochemically demonstrable presence of the noradrenergic and cholinergic enzymes tyrosine hydroxylase (TH) and choline acetyltransferase (ChAT), respectively, and the synthesis of the corresponding neurotransmitters in embryonic quail sympathetic neuronal and non-neuronal cells purified by fluorescence-activated cell sorting. We show that (1) freshly sorted neurons synthesize both NAd and ACh, whereas non-neuronal cells produce neither; (2) the overwhelming majority of the sympathetic neurons display TH immunoreactivity; (3) about half of the TH-positive neurons are recognized by an anti-ChAT antibody in an artificial medium that selectively enhances synthesis and/or accumulation of ACh; (4) the non-neuronal cells are important for survival of the neurons and potentiate their synthesis of ACh in this medium, and (5) finally, we present evidence that expression of TH in noradrenergic neurons and in small intensely fluorescent cells of sympathetic ganglia is differentially regulated.

Animals↗

PubMed1992

Phenotypic plasticity for life-history traits in Drosophila melanogaster. III. Effect of the environment on genetic parameters.

We estimated genetic and environmental variance components for developmental time and dry weight at eclosion in Drosophila melanogaster raised in ten different environments (all combinations of 22, 25 and 28 degrees C and 0.5, 1 and 4% yeast concentration, and 0.25% yeast at 25 degrees C). We used six homozygous lines derived from a natural population for complete diallel crosses in each environment. Additive genetic variances were consistently low for both traits (h2 around 10%). The additive genetic variance of developmental time was larger at lower yeast concentrations, but the heritability did not increase because other components were also larger. The additive genetic effects of the six parental lines changed ranks across environments, suggesting a mechanism for the maintenance of genetic variation in heterogenous environments. The variance due to non-directional dominance was small in most environments. However, there was directional dominance in the form of inbreeding depression for both traits. It was pronounced at high yeast levels and temperatures but disappeared when yeast or temperature were decreased. This meant that the heterozygous flies were more sensitive to environmental differences than homozygous flies. Because dominance effects are not heritable, this suggests that the evolution of plasticity can be constrained when dominance effects are important as a mechanism for plasticity.

Adaptation, Physiological↗

PubMed2026

Spatiotemporal single-cell profiling reveals T cell clonal dynamics and phenotypic plasticity in human graft-versus-host disease.

Allogeneic hematopoietic cell transplantation cures hematologic diseases but is limited by acute graft‑versus‑host disease. How human T cell clones drive epithelial injury remains poorly mapped. We studied 31 transplant recipients, integrating longitudinal T cell antigen receptor (TCR) profiling with single-cell RNA sequencing/TCR sequencing and spatial transcriptomics to track T cell clonal dynamics. We developed DecompTCR to resolve temporal dynamics and adapted computational tools to map clone phenotypes and niches in tissue. Our analyses revealed that cyclophosphamide selectively depletes alloreactive clones, although insufficient early expansion leads to incomplete depletion and severe disease. Severe graft‑versus‑host disease is marked by persistent expansion of alloreactive clones, rewiring of homeostatic cell types and diversification of donor-derived CD8+ clonotypes that acquire Hobit (ZNF683)+ tissue‑resident memory T (TRM) cell programs during migration to epithelium. Spatial deconvolution identified CD8+ effector/Hobit+ TRM hubs near intestinal stem‑cell-rich crypt bases and crypt‑loss regions. This clonotype‑resolved framework links tissue‑instructed TRM cell remodeling to localized epithelial injury, nominating early-repertoire dynamics and spatial hub burden as biomarkers.

Journal Article↗

PubMedDate not supplied

Eimerians in harvest mice, Reithrodontomys spp., from Mexico, California and New Mexico, and phenotypic plasticity in oocysts of Eimeria arizonensis.

Between May 1979 and August 1991, 48.7% (57/117) of the harvest mice (Reithrodontomys spp.) examined from 10 localities in Mexico, California and New Mexico had coccidian oocysts in their feces. A total of 46.7% (49/105) of the Reithrodontomys megalotis examined were positive for coccidian oocysts; this included samples from five states in Mexico (47.1%, 8/17), three counties in California (66.7%, 4/6) and two counties in New Mexico (45.1%, 37/82); 66.7% (8/12) of the Reithrodontomys montanus from one county in New Mexico also were infected. Only two coccidian species, Eimeria arizonensis and Eimeria langebarteli, were found in these hosts. Oocysts of E. langebarteli were found only in R. megalotis: in all three infected mice from Madera County, California, in the only mouse from San Bernardino County, California, and in 63% (5/8) of the infected mice from four states in Mexico. Oocysts of E. arizonensis were found in R. megalotis in Mexico, California, and New Mexico and in R. montanus from New Mexico. Sporulated oocysts of E. langebarteli differed slightly from those in previously published reports by having wider oocysts and larger sporocysts. Sporulated oocysts of E. arizonensis were variable in size, with those recovered from R. montanus significantly larger in length and width and sporocyst width than those from R. megalotis. The structure of the oocyst residuum was polymorphic, both within and between host species, and within the same mouse; it could appear as one large globule, two globules, several to many smaller globules, or as a compact mass of many small granules. Oocysts with a variable residuum were larger than those with one globule in all oocyst/sporocyst dimensions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed2026

Coral color morphs exhibit distinct microbial and proteomic profiles linked to stress and immune mechanisms in a changing ocean.

BACKGROUND: Coral phenotypic plasticity facilitates acclimation and adaptation to environmental variability. Coral species often display a variety of color morphs, yet key biological and ecological implications of such phenotypic variation remain underexplored. Here, we present the first proteomic and untargeted lipidomic and metabolomic survey to explore the biological characteristics and potential ecological significance of different color morphs (pink and brown) of healthy Pocillopora verrucosa sampled along a latitudinal gradient. RESULTS: Our multi-omic approach elucidated distinct mechanisms associated with these dominant color morphs. We discovered bacterial indicators specific to each morph: putative pathogens such as Salmonella, Escherichia-Shigella, and carotenoid-producing Gemmatimonas were notably associated with the pink morph, whereas the brown morph was associated with potentially beneficial bacteria, such as Lysobacter, Acinetobacter, and Endozoicomonas. Despite these microbiome differences, the lipidome and metabolome of P. verrucosa were surprisingly homogeneous across colors and locations, suggesting similar metabolic performances during summer conditions. Key polar and apolar lipid classes, such as fatty acids, glycerophosphocholines, and retinoids, were prevalent. Notably, our proteomic analysis revealed morph-specific expressions, with pink morphs exhibiting enhanced levels of GFP-like proteins, Ankyrin, and the enzyme pullulanase, suggesting novel putative protective roles. In contrast, the brown morphs showed a higher abundance of heat shock proteins, indicating putative differential stress response capabilities. CONCLUSION: This comprehensive study provides the first proteomic survey of P. verrucosa and identifies key physiological pathways and trade-offs linked to color morphs, which can further contribute to enhancing our understanding of coral resilience in the face of climate change. SIGNIFICANCE STATEMENT: Understanding the phenotypic plasticity of corals is crucial for uncovering mechanisms of resilience in warming oceans, yet the biological significance of coral color morphs still needs to be explored. Using an innovative multi-omic approach (proteomics, lipidomics, and metabolomics), we provide the first comprehensive analysis of differences between pink and brown morphs of Pocillopora verrucosa. Our data reveal key taxa, potentially pathogenic or beneficial, associated with each morph, and suggest different strategies for each color morph to cope with heat stress, either expressing proteins involved in UV protection and heterotrophic activity or enhanced levels of heat stress resilience and DNA repair. These findings offer insights into the phenotypic plasticity of coral color morphs and their differential responses to climate change. Video Abstract.

Anthozoa↗

PubMed2026

The Multiple Roles of Genetics on Freshwater Macrophyte Functional Traits in the Interplay With the Environment: A Review.

The study of functional trait variation is increasingly used to understand macrophyte adaptation, as traits reflect organismal performance under different ecosystem conditions. Phenotypic expression results from the interplay of genetic and environmental factors: genetics provides the molecular basis for heritable traits and constrains potential phenotypes, while the environment acts as a selective and modulatory force. However, the genetic insight into traits has rarely been addressed in freshwater macrophyte studies. This review examines the different ways in which the DNA of macrophytes interplays with the environment and contributes to the variation in their functional traits, outlining main approaches, gaps, and future challenges. Only 21 studies explicitly combined genetics with functional traits and environment in the last fifteen years. The most common approach was the use of common garden experiments to explore acclimation and adaptation in a few model species. Current studies mainly focus on morphological and growth traits that best describe macrophytes' economic strategies, with limited attention to other trait categories, while the genetic and DNA traits studied are more variable. Across studies, environmental factors generally explained a larger proportion of functional trait variation, highlighting the dominant role of phenotypic plasticity for macrophyte acclimatation, whereas genetic contribution increased under experimentally manipulated conditions. Genome size and epigenetic variation influenced phenotypic plasticity; however, the effect was different and inconsistent on traits and depended on phylogenetic relationships and geographical environment variation. In field studies of natural populations, life history traits and hydrology had a strong effect on the geographic distribution of genetic diversity and the response to selection, as well as on our ability to distinguish selection from genetic drift. Future research should enhance molecular analyses, adopt multifactorial and long-term experimental designs, develop conceptual frameworks to address the relationships between genomics, environment and functional traits and integrate emerging tools to capture macrophyte adaptation better.

adaptation↗

PubMed2026

Maternal and developmental temperature modulate adult response to temperature in Drosophila melanogaster.

Beyond inherited genes and environmentally induced changes in gene expression, phenotypes can also be shaped by parental effects-an effect from a parental phenotype that causes modifications in offspring traits, which cannot be solely explained by the parental or offspring genomes. Such effects may prepare offspring for future environmental conditions and contribute to phenotypic plasticity, including responses to temperature. While temperature-induced plasticity has been extensively studied, the relative contributions of parental versus direct environmental cues remain poorly understood. The fruit fly Drosophila melanogaster is a powerful model for studying physiological and behavioral adaptation to temperature. Flies inhabit environments spanning broad thermal ranges and show evidence of parental effects, such as increased heat tolerance in offspring from warm-reared parents. Here, we exposed mothers to two experimental temperatures and split their broods between the same two temperatures to estimate the relative importance of maternal and developmental effects on adult physiological and developmental responses to temperature. We find that the reaction norms of locomotor activity under gradually increasing temperatures, responses to heat-shock and cold-shock, and fecundity are mostly governed by direct plastic responses to developmental environment. We detected comparatively weak maternal effects in the response to heat-shock, fecundity, and grand-offspring survival where matched environments counteracted the effects of direct offspring experience. We conclude that thermal experience during development is the primary determinant of phenotypic plasticity in D. melanogaster, while maternal experience contributes a small but non-negligible component.

Animals↗

PubMed2025

Whole Genome Sequencing Reveals How Plasticity and Genetic Differentiation Underlie Sympatric Morphs of Arctic Charr.

Salmonids have a remarkable ability to form sympatric morphs after postglacial colonisation of freshwater lakes. These morphs often differ in morphology, feeding and spawning behaviour. Here, we explored the genetic basis of morph differentiation in Arctic charr (n = 283) by first establishing a high-quality reference genome and then using this in whole genome sequencing of distinct morphs present in two Norwegian and two Icelandic lakes. The four lakes represent the spectrum of genetic differentiation between morphs from one lake with no genetic differentiation between morphs, implying phenotypic plasticity, to two lakes with locus-specific genetic differentiation, implying incomplete reproductive isolation, and one lake with strong genome-wide divergence consistent with complete reproductive isolation. As many as 12 putative inversions ranging from 0.45 to 3.25 Mbp in size segregated among the four morphs present in one lake, Thingvallavatn, and these contributed significantly to the genetic differentiation among morphs. None of the putative inversions were found in any of the other lakes, but there were cases of partial haplotype sharing in similar morph contrasts in other lakes. Our findings are consistent with a highly polygenic basis of morph differentiation with population-specific selection on alleles linked to the development of similar morph phenotypes. The results support a model where morph differentiation is first established through phenotypic plasticity, leading to niche expansion and separation. This may be followed by gradual development of reproductive isolation, locus-specific differentiation and eventually complete reproductive isolation and genome-wide divergence.

Whole Genome Sequencing↗

PubMed2025

Silent cells? Potential for context-dependent gene expression in mature sperm.

Sperm are traditionally viewed as transcriptionally and translationally silent cells. However, observations that components of the cellular machinery of gene expression are maintained in ejaculated sperm are increasingly cited as challenges to this fundamental assumption. Here, we critically evaluate these arguments and present three lines of evidence from both model and non-model systems that collectively raise the question of whether ejaculated sperm may be capable of active gene expression. First, and critical for arguments surrounding the possibility of differential gene expression, we review recent evidence that spermatozoa may retain the capacity to transcribe and translate their genomes. Second, we highlight how sperm cells can exhibit differential transcript quantities across different post-ejaculation environments. Third, we ask whether the accumulating evidence of remarkable phenotypic plasticity in post-ejaculatory sperm phenotypes could be mechanistically underpinned by changes in sperm gene expression. While these lines of evidence are indirect and do not definitively show transcription of sperm genomes, we highlight how emerging technologies may enable us to test this hypothesis explicitly. Our review advocates for progress in this field and highlights several important evolutionary, ecological and practical implications that will probably transcend disciplines to the clinical and applied reproductive sectors.

Male↗

PubMed2026

Stress-driven strategic games in cancer.

Tumor cells face chronic genotoxic, metabolic, hypoxic, and immune stress that shapes their evolution. While stress-response molecular pathways are well characterized, cancer biology lacks a predictive framework for how cells select among alternative adaptive strategies and how these selections interact to produce tumor-level behavior. We propose that evolutionary game theory, previously applied to cooperation in cancer, should be extended to position stress adaptation itself as the organizing principle of tumor evolution. In this framework, stress-adaptive strategies constitute frequency-dependent games whose payoffs depend on population composition. We introduce a three-level distinction between cell states (transcriptional snapshots), game states (local configurations of stress and neighbor composition that define the active payoff structure), and cell strategies (conditional behavioral policies mapping game states to fitness-relevant outputs). This perspective explains the maintenance of intratumor heterogeneity through frequency-dependent selection, the reversibility of resistance through bet-hedging dynamics, and therapy resistance as an equilibrium outcome rather than genetic inevitability. Integrating insights from single-cell genomics, spatial profiling, and lineage tracing, we outline testable predictions and experimental approaches for measuring payoff structures. Therapeutically, the framework suggests exploiting adaptive trade-offs, restricting phenotypic plasticity, and reshaping competitive landscapes. Re-framing cancer as an evolving game of stress adaptation provides a unifying structure for predictive oncology.

Animals↗

PubMed2026

Adaptations to breath-hold diving: from traditional divers to elite athletes.

Breath-hold diving exposes humans to repeated episodes of profound hypoxia and hypercapnia, eliciting physiological adaptations that enable prolonged underwater performance. This article summarises current knowledge on chronic adaptations in elite breath-hold athletes and traditional diving populations, including the Bajau sea nomads of Southeast Asia and the Korean Haenyeo divers. Evidence indicates that repeated apnoea induces adaptations across multiple physiological systems. Haematological changes include increased spleen size and enhanced splenic contraction, augmenting circulating haemoglobin and oxygen stores during apnoea. In elite divers, structured training can increase resting spleen volume, whereas the Bajau exhibit genetically associated splenic enlargement linked to variants near the PDE10A gene. Cardiopulmonary adaptations include modified pulmonary vascular responses to hypoxia, improved oxygen conservation, and metabolic shifts favoring efficient mitochondrial energy production. Molecular adaptations involve enhanced antioxidant defenses and activation of hypoxia-responsive pathways that may mitigate oxidative stress associated with repeated hypoxia-reoxygenation cycles. Emerging evidence also suggests neural plasticity and possible structural brain adaptations, although the long-term neurological consequences of chronic intermittent hypoxia exposure remain uncertain. Studies of traditional diving populations indicate that both phenotypic plasticity and genetic selection contribute to diving capacity, highlighting interactions between training and evolution. Despite these benefits, breath-hold diving also carries risks, including hypoxic blackout, decompression sickness, and potential neurological injury. Understanding the mechanisms underlying human tolerance to extreme hypoxia may have implications beyond diving physiology, including applications in cardiovascular medicine, hypoxic diseases, and rehabilitation. Further longitudinal, genomic, and mechanistic studies are needed to clarify the limits, benefits, and clinical relevance of these adaptations.

Humans↗

PubMed2024

A Proteogenomic Pipeline for the Analysis of Protein Biosynthesis Errors in the Human Pathogen Candida albicans.

Candida albicans is a diploid pathogen known for its ability to live as a commensal fungus in healthy individuals but causing both superficial infections and disseminated candidiasis in immunocompromised patients where it is associated with high morbidity and mortality. Its success in colonizing the human host is attributed to a wide range of virulence traits that modulate interactions between the host and the pathogen, such as optimal growth rate at 37 °C, the ability to switch between yeast and hyphal forms, and a remarkable genomic and phenotypic plasticity. A fascinating aspect of its biology is a prominent heterogeneous proteome that arises from frequent genomic rearrangements, high allelic variation, and high levels of amino acid misincorporations in proteins. This leads to increased morphological and physiological phenotypic diversity of high adaptive potential, but the scope of such protein mistranslation is poorly understood due to technical difficulties in detecting and quantifying amino acid misincorporation events in complex protein samples. We have developed and optimized mass spectrometry and bioinformatics pipelines capable of identifying rare amino acid misincorporation events at the proteome level. We have also analyzed the proteomic profile of an engineered C. albicans strain that exhibits high level of leucine misincorporation at protein CUG sites and employed an in vivo quantitative gain-of-function fluorescence reporter system to validate our LC-MS/MS data. C. albicans misincorporates amino acids above the background level at protein sites of diverse codons, particularly at CUG, confirming our previous data on the quantification of leucine incorporation at single CUG sites of recombinant reporter proteins, but increasing misincorporation of Leucine at these sites does not alter the translational fidelity of the other codons. These findings indicate that the C. albicans statistical proteome exceeds prior estimates, suggesting that its highly plastic phenome may also be modulated by environmental factors due to translational ambiguity.

Candida albicans↗

PubMed2025

Machine learning on multiple epigenetic features reveals H3K27Ac as a driver of gene expression prediction across patients with glioblastoma.

Epigenetic mechanisms play a crucial role in driving transcript expression and shaping the phenotypic plasticity of glioblastoma stem cells (GSCs), contributing to tumor heterogeneity and therapeutic resistance. These mechanisms dynamically regulate the expression of key oncogenic and stemness-associated genes, enabling GSCs to adapt to environmental cues and evade targeted therapies. Importantly, epigenetic reprogramming allows GSCs to transition between cellular states, including therapy-resistant mesenchymal-like phenotypes, underscoring the need for epigenetic-targeting strategies to disrupt these adaptive processes. Understanding these epigenetic drivers of gene expression provides a foundation for novel therapeutic interventions aimed at eradicating GSCs and improving glioblastoma outcomes. Using machine learning (ML), we employ cross-patient prediction of transcript expression in GSCs by combining epigenetic features from various sources, including ATAC-seq, CTCF ChIP-seq, RNAPII ChIP-seq, H3K27Ac ChIP-seq, and RNA-seq. We investigate different ML and deep learning (DL) models for this task and ultimately build our final pipeline using XGBoost. The model trained on one patient generalizes to other 11 patients with high performance. Notably, H3K27Ac alone from a single patient is sufficient to predict gene expression in all 11 patients. Furthermore, the distribution of H3K27Ac peaks across the genomes of all patients is remarkably similar. These findings suggest that GSCs share a common distributional pattern of enhancer activity characterized by H3K27Ac, which can be utilized to predict gene expression in GSCs across patients. In summary, while GSCs are known for their transcriptomic and phenotypic heterogeneity, we propose that they share a common epigenetic pattern of enhancer activation that defines their underlying transcriptomic expression pattern. This pattern can predict gene expression across patient samples, providing valuable insights into the biology of GSCs.

Glioblastoma↗

PubMed1992

Interaction with basement membrane serves to rapidly distinguish growth and differentiation pattern of normal and malignant human breast epithelial cells.

Normal human breast epithelial cells show a high degree of phenotypic plasticity in monolayer culture and express many traits that otherwise characterize tumor cells in vivo. Paradoxically, primary human breast carcinoma cells are difficult to establish in culture: most outgrowths arise from the normal tissue surrounding the tumor. These characteristics have posed major obstacles to the establishment of simple reliable criteria for mammary epithelial transformation in culture. In the present study, we show that a reconstituted basement membrane (BM) can be used to culture all normal human breast epithelial cells and a subset of human breast carcinoma cells. The two cell types can be readily distinguished by virtue of the ability of normal cells to reexpress a structurally and functionally differentiated phenotype within BM. Twelve specimens of normal breast tissue and 2 normal breast epithelial cell lines (total 14 samples) embedded in BM as single cells were able to form multicellular spherical colonies with a final size close to that of true acini in situ. Sections of mature spheres revealed a central lumen surrounded by polarized luminal epithelial cells expressing keratins 18 and 19 and sialomucin at the apical membrane. Significantly, two-thirds of normal spheres deposited a visible endogenous type IV collagen-containing BM even though they were in contact with exogenously provided BM. Growth was arrested completely within the same time period. In contrast, none of 6 carcinoma cell lines or 2 cultures of carcinoma from fresh samples (total 8 samples) responded to BM by growth regulation, lumen formation, correct polarity, or deposition of endogenous BM. These findings may provide the basis of a rapid assay for discriminating normal human breast epithelial cells from their malignant counterparts. Furthermore, we propose that the ability to sense BM appropriately and to form three-dimensional organotypic structures may be the function of a class of "suppressor" genes that are lost as cells become malignant.

Basement Membrane↗

PubMed2025

Multiomics Reveal Associations Between CpG Methylation, Histone Modifications and Transcription in a Species That has Lost DNMT3, the Colorado Potato Beetle.

Insects display exceptional phenotypic plasticity, which can be mediated by epigenetic modifications, including CpG methylation and histone modifications. In vertebrates, both are interlinked and CpG methylation is associated with gene repression. However, little is known about these regulatory systems in invertebrates, where CpG methylation is mainly restricted to gene bodies of transcriptionally active genes. A widely conserved mechanism involves the co-transcriptional deposition of H3K36 trimethylation and the targeted methylation of unmethylated CpGs by the de novo DNA methyltransferase DNMT3. However, DNMT3 has been lost multiple times in invertebrate lineages raising the question of how the links between CpG methylation, histone modifications and gene expression are affected by its loss. Here, we report the epigenetic landscape of Leptinotarsa decemlineata, a beetle species that has lost DNMT3 but retained CpG methylation. We combine RNA-seq, enzymatic methyl-seq and CUT&Tag to study gene expression, CpG methylation and patterns of H3K36me3 and H3K27ac histone modifications on a genome-wide scale. Despite the loss of DNMT3, H3K36me3 mirrors CpG methylation patterns. Together, they give rise to signature profiles for expressed and not expressed genes. H3K27ac patterns show a prominent peak at the transcription start site that is predictive of expressed genes irrespective of their methylation status. Our study provides new insights into the evolutionary flexibility of epigenetic modification systems that urge caution when generalizing across species.

Animals↗

PubMed2026

Overcoming cancer resistance in pancreatic cancer: toward dynamic precision oncology.

Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal malignancy, largely because of its profound and evolving therapeutic resistance. Resistance is not determined by a single molecular alteration but arises from interconnected mechanisms, including intrinsic resistance, treatment-induced adaptive resistance, acquired resistance, genomic evolution, clonal selection, cancer stemness, phenotypic plasticity, metabolic adaptation, and tumor microenvironment-mediated effects. Emerging therapeutic approaches targeting KRAS/RAS signaling, stromal and immune components, metabolic dependencies, and DNA damage repair pathways offer opportunities to address these mechanisms, although durable efficacy remains limited by biological heterogeneity and adaptive responses. In this review, we examine therapeutic resistance as an evolutionary and multidimensional process and summarize emerging strategies for overcoming resistance. We further propose a Dynamic Precision Oncology (DPO) framework that extends conventional precision oncology beyond baseline molecular profiling by integrating longitudinal assessment of tumor genomics, circulating tumor DNA, CA19-9, imaging, radiomics, and clinical characteristics. This framework emphasizes iterative detection and characterization of emerging resistance, mechanism-informed treatment adaptation, and subsequent reassessment rather than automatic treatment modification based on a single biomarker. DPO may provide a conceptual framework for integrating evolving tumor biology into treatment decision-making, while prospective studies are needed to validate biomarkers, define actionable thresholds, and determine whether longitudinal resistance-guided strategies improve clinical outcomes in PDAC.

Humans↗

PubMed2026

The Brazilian contribution to ant toxinology: challenges and perspectives.

Ant toxinology in Brazil is a small but growing field that has revealed wide biochemical diversity and clear potential for bioprospecting therapeutic molecules. This review compiles the Brazilian contribution, focusing on advances in the characterization of venoms from medically and ecologically important species of Dinoponera, Solenopsis, Paraponera, Pachycondyla, Neoponera, and Ectatomma. Brazilian groups applied omics approaches, including transcriptomics and proteomics, to resolve the composition of these venoms and identified peptide-rich arsenals with antimicrobial, antiparasitic, antitumor, and neuroactive activity. Studies of venom phenotypic plasticity showed ecological factors such as diet and seasonality shape venom composition. Two challenges persist: assigning function to still unidentified components and obtaining venom in the quantities that broad analysis requires. The near-term prospects are the rational design of peptide analogues with improved activity and continued bioprospecting of new species, which together position Brazil as a central contributor to ant toxinology.

Animals↗