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PubMed2026

Immune cell-specific genetic architecture of Alzheimer's disease revealed by multi-omics analysis for therapeutic target discovery and prioritization.

Alzheimer's disease (AD) is a multifactorial neurodegenerative condition in which accumulating genetic and molecular evidence implicates dysregulation of peripheral immune processes in disease pathogenesis. Nevertheless, the contribution of distinct peripheral immune cell subsets and associated gene regulatory landscapes to AD risk remains incompletely defined. To address this gap, we integrated single-cell expression quantitative trait loci (sc‑eQTL) data from the OneK1K cohort with AD GWAS summary statistics. We systematically interrogated immune cell-specific genes for their contributions to AD risk by integrating genetic causal inference with Bayesian colocalization analyses, and identified 24 eGenes that passed both the MR significance threshold (P < 0.05) and the criterion for strong shared genetic signals (PP.H4 > 0.8). Notable candidates included GATS, HLA-DOB, HLA-DQA1, PM20D1, and others, with each gene demonstrating a cell-type-specific association restricted to its corresponding immune cell type, such as monocytes, CD8 + T cells, or B cells. Independent peripheral blood single-cell transcriptomic data further supported disease-associated shifts in cell-type-specific expression patterns in AD. Phenome-wide association studies (PheWAS) indicated limited associations with off-target traits, indicating a favorable safety profile for therapeutic intervention, with the exceptions of B4GALNT3, PM20D1, and CNN2. Integration of immune gene targets with pharmacological databases yielded three candidate compound, including NSC321521 (targeting HLA-DQA1), phenoxybenzamine (targeting GSTP1), and rimexolone (targeting BIN1). Among these compounds, Predicted blood-brain barrier permeability was observed only for phenoxybenzamine and rimexolone, with docking studies indicating stable interactions, such as those between NSC321521 and HLA-DQA1, phenoxybenzamine and GSTP1, and rimexolone and BIN1. This integrative approach highlights key immune‑cell‑specific genes involved in AD and proposes repurposable drugs with central nervous system potential, paving the way for more targeted immunomodulatory strategies in AD.

Humans↗

PubMed2025

Integration of therapeutic cargo into the human genome with programmable type V-K CAST.

CRISPR-associated (Cas) transposases (CAST) are RNA-guided systems capable of programmable integration of large segments of DNA without creating double-strand breaks. Engineered Cascade CAST function in human cells but are challenging to deploy due to the complexity of the targeting components. Unlike Cascade, which require three Cas proteins, type V-K CAST require a single Cas12k effector for targeting. Here, we show that compact type V-K CAST from uncultivated microbes are repurposable for programmable DNA integration into the genome of human cells. Engineering for nuclear localization and function enables integration of a therapeutically relevant transgene at a safe-harbor site in multiple human cell types. Notably, off-targets are rare events reproducibly found in specific genomic regions. These CAST advancements are expected to accelerate applications of genome editing to therapeutic development, biotechnology, and synthetic biology.

Humans↗

PubMed2026

Yellow protein co-opted to sustain obligate symbiosis in leaf beetles.

Yellow proteins are best known for their roles in pigmentation, behavior, and development across insects. Here, we uncover their striking evolutionary co-option for a wholly distinct function: sustaining a Paleocene-aged digestive symbiosis in tortoise beetles. We show that a female-specific Yellow forms the gelatinous spheres that encapsulate the bacterium Stammera during vertical transmission, allowing it to subsist extracellularly despite its drastically reduced genome (0.24 Mb) and limited metabolic capacity. Yellow expression is highly localized to symbiont-harboring glands in the ovaries, where the protein is assembled into a matrix and secreted during egg-laying. Functional knockdown of yellow disrupts sphere integrity and compromises symbiont viability under dry conditions, underscoring the protein's embedding properties and protective role for Stammera. These findings reveal a novel function for an ancient gene family and demonstrate how tortoise beetles have repurposed Yellows to overcome the extreme metabolic constraints faced by their symbionts during extracellular transmission.

Animals↗

PubMed2026

HDAC inhibition via suberoylanilide hydroxamic acid ameliorates doxorubicin-induced cardiotoxicity.

Anthracycline-induced cardiotoxicity remains a major limitation of cancer therapy, and effective preventive strategies are lacking. Topoisomerase IIb has been implicated as a central driver of this toxicity, suggesting that epigenetic regulators may interfere with the pathological cardiac response. Here, we show that doxorubicin promotes topoisomerase IIb accumulation at cardiomyocyte-specific gene promoters (e.g., Actc1, Myl2, and Myh7) overlapping myocyte enhancer factor 2 binding sites and enhances myocyte enhancer factor 2 -dependent transcription. This response is attenuated by the pan-histone deacetylase inhibitor suberoylanilide hydroxamic acid. Suberoylanilide hydroxamic acid -mediated cardioprotection requires class IIa histone deacetylases, as genetic loss of HDAC4 abolishes its effect. Mechanistically, suberoylanilide hydroxamic acid induces acetylation of the chaperone 14-3-3, disrupting its interaction with HDAC4/5, promoting their nuclear accumulation, and repressing myocyte enhancer factor 2 - driven transcription. In vivo, suberoylanilide hydroxamic acid mitigates doxorubicin-induced cardiotoxicity. These findings identify histone deacetylase inhibition as a cardioprotective repurposing strategy and reveal a mechanistic link between epigenetic regulation and anthracycline-associated cardiotoxicity.

Doxorubicin↗

PubMed2026

Cell type-selective targeting by heterobifunctional protein binders via in-cell enrichment.

Non-catalytic heterobifunctional protein binders promise to expand the range of therapeutic options by establishing complexes between key target proteins and accessory presenter proteins equipped with additional properties. Here, we systematically investigate the rational design of such molecules, explore the biochemical basis of complex formation and determine how they achieve cellular efficacy using the endogenously expressed immunophilin FKBP12 as presenter protein and the transcriptional regulator BRD4 as target protein. We present classes of bifunctional molecules that enable selective, FKBP12-dependent killing of specific cell types at subnanomolar concentrations and allow to differentiate between closely related bromodomains of the BET family. We propose that the strongly potentiated efficacy of these bifunctional compounds is based on cellular enrichment through binding to the highly abundant presenter protein FKBP12, a mechanism we term "CellTrap". Our findings substantiate the concept that highly expressed, non-essential proteins can be repurposed as selective recruiters to expand therapeutic windows of existing small-molecule inhibitors, opening new avenues for designing targeted drugs with improved cell-type specificity.

Tacrolimus Binding Protein 1A↗

PubMed2026

Programmable enzymes for targeted gene insertion.

Genome editing technologies have advanced from nuclease-based reagents that generate programmed DNA double-strand breaks, which can cause deleterious effects, to next-generation reagents that perform controlled DNA modification through double-strand break-independent mechanisms, such as base editing and prime editing. Although these approaches enable precise small-scale sequence changes, methods for programmable insertion of large DNA cargos have been limited. The ability to write entire genes or large regions into the genome could transform the treatment of genetically heterogeneous disorders, for which numerous pathogenic variants underlie a common disease and mutation-specific editing strategies are impractical. Recent advances in computational genome mining have accelerated the discovery of naturally occurring enzymes with novel biochemical and functional properties, including recombinases and transposases capable of large-scale modifications. Moreover, directed evolution, rational engineering and expanded homologue discovery are enabling the repurposing and optimization of these systems for genome engineering. Here we review recent technology development efforts that harness diverse enzymes for kilobase-scale genome engineering, with a particular focus on CRISPR-associated transposase systems.

Journal Article↗

PubMed2026

Inhibiting cyclin D1-CDK6 suppresses senescence-associated inflammatory gene expression and age-related functional decline.

Cellular senescence contributes to aging and age-related diseases by driving chronic inflammation through the senescence-associated secretory phenotype (SASP), including interferon-stimulated genes (ISGs). Here we confirm and extend previous observations that cyclin D1 (CCND1), a key cell cycle regulator, is paradoxically upregulated across models of nonproliferating senescent cells. We show that CCND1 and its kinase partner CDK6 drive SASP and ISG expression in senescent cells by promoting DNA damage accumulation. This leads to the formation of cytoplasmic chromatin fragments that activate pro-inflammatory cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling. In aged mouse livers, senescent hepatocytes show increased Ccnd1 expression. Hepatocyte-specific Ccnd1 knockout or treatment with the clinical grade CDK4/6 inhibitor palbociclib reduces DNA damage and ISGs in aged mouse liver. Further, palbociclib suppresses frailty and improves physical performance of aged mice. These findings demonstrate a role for CCND1/CDK6 in regulating DNA damage and inflammation in senescence and aging, highlighting it as a promising target for therapeutic repurposing.

Animals↗

PubMed2024

Intranasal neomycin evokes broad-spectrum antiviral immunity in the upper respiratory tract.

Respiratory virus infections in humans cause a broad-spectrum of diseases that result in substantial morbidity and mortality annually worldwide. To reduce the global burden of respiratory viral diseases, preventative and therapeutic interventions that are accessible and effective are urgently needed, especially in countries that are disproportionately affected. Repurposing generic medicine has the potential to bring new treatments for infectious diseases to patients efficiently and equitably. In this study, we found that intranasal delivery of neomycin, a generic aminoglycoside antibiotic, induces the expression of interferon-stimulated genes (ISGs) in the nasal mucosa that is independent of the commensal microbiota. Prophylactic or therapeutic administration of neomycin provided significant protection against upper respiratory infection and lethal disease in a mouse model of COVID-19. Furthermore, neomycin treatment protected Mx1 congenic mice from upper and lower respiratory infections with a highly virulent strain of influenza A virus. In Syrian hamsters, neomycin treatment potently mitigated contact transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In healthy humans, intranasal application of neomycin-containing Neosporin ointment was well tolerated and effective at inducing ISG expression in the nose in a subset of participants. These findings suggest that neomycin has the potential to be harnessed as a host-directed antiviral strategy for the prevention and treatment of respiratory viral infections.

Animals↗

PubMed2025

Identification of maternal Gγ(Aγδβ)0 thalassemia through retrospective reanalysis of prenatal cfDNA sequencing data.

OBJECTIVE: Non-invasive prenatal screening (NIPS) is widely used to detect chromosomal abnormalities such as trisomies 21, 13, and 18 and is also effective in screening for copy number variations (CNVs). However, the routine application of NIPS to detect smaller CNVs within the HBB gene, specifically Gγ(Aγδβ)0 thalassemia, has yet to be well documented. This study aims to evaluate the efficacy of cfDNA-based maternal carrier screening in routine screening for Gγ(Aγδβ)0 thalassemia. METHODS: We performed a retrospective analysis of 107,300 pregnant women who underwent NIPS at Longgang Maternal and Child Healthcare Hospital in Shenzhen from December 2017 to May 2022. Using an improved algorithm, we reanalyzed NIPS data to identify maternal Gγ(Aγδβ)0 thalassemia. Positive cases were confirmed by multiplex ligation-dependent probe amplification (MLPA) using peripheral blood leukocytes. RESULTS: Among the 107,300 NIPS analyses, 38 maternal deletion CNVs within the HBB gene were identified using the improved algorithm, with a prevalence of 0.035% (38/107,300). MLPA confirmed that all detected deletions were consistent with Gγ(Aγδβ)0 thalassemia. The positive predictive value (PPV) for detecting Gγ(Aγδβ)0 thalassemia by cfDNA-based maternal carrier screening was 100%. Among the 38 Gγ(Aγδβ)0 cases, 9 were also associated with α-thalassemia deletions, including 4 cases with -SEA/αα, 4 with -α3.7/αα, and 1 with -α4.2/αα. No cases of homozygosity or compound HBB gene variants were observed. CONCLUSIONS: Gγ(Aγδβ)0 thalassemia is not uncommon in China, and repurposed NIPS methodology for maternal genomic analysis in detecting HBB gene deletions is a reliable method for identifying maternal carriers of this disease.

Humans↗

PubMed2026

Integrated multi-omics strategies for identifying novel therapies in psoriasis.

MOTIVATION: Psoriasis is a chronic, immune-mediated disorder with an unmet need for effective treatments. To systematically prioritize therapeutic targets, we integrated proteome-wide Mendelian randomization (MR) with expression validation in blood/skin, genetic susceptibility analysis, differential gene expression (DGE) from bulk and single-cell RNA sequencing (scRNA-seq), colocalization, pathway enrichment, and protein-protein interaction analyses. RESULTS: Proteome-wide MR identified 29 candidate protein targets (Bonferroni-corrected), all replicated in independent datasets. Fifteen targets showed significant expression associations in blood or skin. Eleven proteins-UBLCP1, IL23A, ASF1A, RARRES2, ICAM1, PRSS53, ICAM5, GCA, IL2RA, DBI, and NFKB1-exhibited consistent directional effects with their genes. Genetic susceptibility analysis confirmed 20 target-specific polygenic scores for psoriasis and five for psoriatic arthritis. DGE analysis identified 13 targets in bulk and 13 in scRNA-seq-primarily in keratinocytes and immune cells-with IL2RA, COMP, and A2ML1 dysregulated across both. Colocalization analysis implicated shared causal variants for psoriasis in ASF1A, CD8A, CTF1, IL7R, MMP12, RARRES2, XCL2, DBI, IL23A, IL2RA, SGSH, and TIMD4. Enrichment analyses highlighted involvement in cytotoxicity, immune regulation, and JAK-STAT signaling. Eighteen targets interacted with approved anti-psoriasis drugs. Notably, drugs targeting IL2RA, IL7R, CTF1, ICAM1, MMP12, NFKB1, CD8A, DDX58, IL12A, SGSH, and FAP are approved or in trials for other diseases, suggesting repurposing potential. Our integrative multi-omics approach prioritized 29 high-confidence targets, including 13 novel candidates (RARRES2, ASF1A, CTF1, DBI, B3GNT2, CD8A, TIMD4, CRTAM, SGSH, XCL2, DAPK2, A2ML1, and FAP). Several high-priority targets-such as IL2RA, IL23, MMP12, RARRES2, IL7R, and ICAM1-were supported across analytical layers. These findings provide a robust foundation for psoriasis drug development. AVAILABILITY AND IMPLEMENTATION: The code used for the analyses in this manuscript has been archived in Zenodo at [DOI: 10.5281/zenodo.19692128].

Psoriasis↗

PubMed2025

Novel mutations associated with clofazimine resistance in Mycobacterium intracellulare.

BACKGROUND: Clofazimine is a promising repurposed drug for treating Mycobacterium avium-intracellulare complex pulmonary disease, but its resistance mechanisms in Mycobacterium intracellulare remain poorly understood. OBJECTIVE: This study aims to elucidate the resistance mechanisms of M. intracellulare to clofazimine. METHODS: We isolated 36 clofazimine-resistant M. intracellulare mutants in vitro and performed whole-genome sequencing to identify resistance-associated mutations. Gene complementation was used to validate the role of the identified mutations. RESULTS: We identified various mutations in the marR gene (WP_009952290.1) in 61% of clofazimine-resistant mutants by whole-genome sequencing. Mutations were identified in additional genes encoding ssuD (flavin-dependent oxidoreductase, C67A), lppI (membrane lipoprotein, C207 deletion), GMC oxidoreductase (glucose-methanol-choline oxidoreductase, G157 deletion), MASE1 domain-containing protein (C62G) and PPE family protein (222C deletion). Gene complementation experiments demonstrated that introducing the wild-type marR in clofazimine-resistant strain (L72) with marR mutations reduced clofazimine MIC from 1 mg/L to susceptible baseline (0.25 mg/L), confirming its critical role in clofazimine resistance. Notably, the M. intracellulare MarR lacks homology to Mycobacterium tuberculosis MarR family protein Rv0678 (MmpR) involved in clofazimine and bedaquiline resistance but is flanked by non-efflux pump genes (dhmA and doxX), and unlike M. tuberculosis, its mutation does not cause bedaquiline cross-resistance, indicating a different MarR and distinct regulatory mechanism for clofazimine resistance in M. intracellulare. CONCLUSIONS: This work highlights marR as a key determinant of clofazimine resistance in M. intracellulare and underscores the need for further mechanistic studies with implications for rapid molecular detection and effective treatment.

Clofazimine↗

PubMed2026

Post-Translational Modifications in Traumatic Brain Injury: Decoding the Proteomic Landscape and Molecular Mechanisms of Secondary Injury.

Traumatic brain injury (TBI) initiates a complex secondary injury cascade that significantly contributes to long-term neurological deficits, with post-translational modifications (PTMs) emerging as pivotal molecular regulators of this process. Unlike primary mechanical damage, secondary injury evolves over hours to years and involves intricate proteomic alterations that changes in gene expression alone cannot fully explain. PTMs-including phosphorylation, ubiquitination, acetylation, SUMOylation, glycosylation, and emerging modifications such as succinylation, lactylation, and nitrosylation-serve as dynamic molecular switches that fine-tune protein function, stability, localization, and interactions in response to TBI-induced stressors. These modifications play dual roles: they can either promote neuroprotection and recovery or drive pathological processes such as neuronal cell death (via apoptosis, necroptosis, and ferroptosis), neuroinflammation through glial activation and inflammasome signaling, blood-brain barrier disruption, mitochondrial dysfunction, and impaired synaptic plasticity. Critically, extensive crosstalk exists among different PTM pathways-such as the interplay between phosphorylation and ubiquitination in protein degradation or the competitive balance between acetylation and SUMOylation-that collectively shape cellular fate after injury. This nuanced regulatory network presents both challenges and opportunities for therapeutic intervention. Targeting PTM-related enzymes, including kinases, phosphatases, E3 ligases, and histone deacetylases, has shown promise in preclinical models, while novel strategies like Proteolysis-Targeting Chimeras (PROTACs) and repurposed drugs (e.g., metformin, resveratrol) offer innovative avenues for modulating the PTM landscape. Advances in high-throughput proteomics and mass spectrometry are enabling the mapping of TBI-specific PTM signatures across spatiotemporal phases, facilitating the identification of pro-survival versus pro-death modification thresholds. Despite hurdles in clinical translation-such as blood-brain barrier penetration and off-target effects-the growing understanding of PTM dynamics underscores their potential as both biomarkers and therapeutic targets. Future TBI management may thus rely on precision medicine approaches that integrate multi-PTM profiling to guide combination therapies aimed at tipping the balance toward neural repair and functional recovery.

Brain Injuries, Traumatic↗

PubMed2025

Genome-wide association study of adolescent-onset depression.

Adolescent depression is a heritable psychiatric condition with rising global prevalence and severe long-term outcomes, yet its biological underpinnings remain poorly understood. We conducted the first genome-wide association study of adolescent-onset depression, comprising 102,428 cases (diagnosis or clinical symptom thresholds) and 286,911 controls, including diverse ancestries. Cross-ancestry meta-analysis identified 52 independent variants across 17 loci; European-only analysis found 61 variants at 29 loci, with a SNP-based heritability of 9.8%. Comparative analyses revealed two genes unique to adolescent-onset versus lifetime depression, enriched in neuronal subtypes, and two genes as potential drug repurposing targets. Polygenic scores were associated with adolescent-onset depression across ancestries, persistent depression trajectories, more severe outcomes, as well as reduced cortical volume, surface area and white matter integrity. Genetic correlation and Mendelian randomisation analyses support shared genetic liability and causal links with early puberty and modifiable health and behavioural risk factors. These findings uncover novel genetic loci and refine biological pathways underlying adolescent-onset depression, revealing age-specific mechanisms and early intervention opportunities.

Journal Article↗

PubMed2026

Post-Hoc Long-Read Sequencing Links Leukemic Mutation Status to Single-Cell Transcriptomes.

Single-cell RNA-sequencing-based characterization of cells that belong to the neoplastic clone is a major challenge in hematologic neoplasms, where malignant and normal cells coexist. Confident molecular profiling requires simultaneous analysis of gene expression and genetic mutations in individual cells, an ability that is not supported by the standard 10X Genomics workflow. Here, we systematically evaluated the potential and limitations of repurposing amplified cDNA generated during the 10X Genomics 3' workflow for post hoc genotyping of individual cells. We first established a mixed leukemic cell line system comprising one cell line with KIT point mutations and another with the BCR::ABL1 fusion gene. Targeted long-read PacBio sequencing enabled post hoc assignment of mutation data to transcriptionally profiled cells, but recovery differed between targets. Consistent with ambient RNA in microfluidics-based single-cell workflows, mutation-associated transcripts were detected in cells not expected to carry the corresponding mutations, illustrating how transcript recovery complicates cell-level genotype assignment. Target-specific thresholds mitigated this source of misclassification. In primary chronic myeloid leukemia samples, the post hoc approach detected BCR::ABL1-positive cells at diagnosis, but not during imatinib treatment. Together, we present a framework for adding mutation status to cells already profiled using the 10X Genomics workflow and highlight broader considerations for transcript-based single-cell genotyping.

BCR::ABL1↗

PubMed2026

Context matters: coordinated transcriptional regulation and root plasticity under multinutrient conditions.

Plants often encounter simultaneous imbalances in multiple nutrients, but the regulatory logic coordinating their responses remains poorly understood. We aimed to uncover shared transcriptional programs and regulatory nodes underpinning multinutrient adaptation in Arabidopsis thaliana roots. We analyzed publicly available RNA-seq datasets spanning 15 nutrient and beneficial element conditions using differential expression, co-expression network (WGCNA), and gene regulatory network analysis. Selected transcription factors (TFs) were validated via root phenotyping, suberin staining, and ionomic profiling under two-nutrient stress conditions. We identified a core set of 2050 genes responsive to multiple nutrient treatments, enriched for suberin biosynthesis, and structured into modular co-expression clusters. Eight prioritized candidate TFs (ARR10, GBF3, HHO5, NAC32, NF-YA3, NF-YB2, SARD1, and WRKY33) were shown to modulate root system architecture under specific nutrient combinations. WRKY33 and NF-YB2, in particular, regulated nutrient-responsive suberin deposition and ionomic plasticity. These findings reveal suberin remodeling as a shared downstream process in multinutrient responses and suggest that plasticity is not a fixed trait but a modular, polygenic, and context-dependent outcome. Repurposed TFs with pleiotropic functions coordinate structural and physiological traits, providing regulatory entry points for improving nutrient resilience.

Plant Roots↗

PubMed2025

Transcriptomic and enzymological evidence for plastid peptidoglycan synthesis in the gymnosperm Picea abies.

It is understood that a cyanobacterium was the progenitor of plastids and that the biosynthesis of cell wall peptidoglycan was lost during chloroplast evolution. However, accumulated data, especially from the moss Physcomitrium patens, suggest that peptidoglycan remains essential for plastid division in some land plants. A fundamental set of peptidoglycan biosynthesis (Mur) genes has been identified in the genomes of these land plants, while many angiosperms no longer encode some core Mur genes, including a bifunctional penicillin-binding protein (PBP). Ten incomplete Mur genes were previously identified in the genome of the gymnosperm Picea abies but these could be pseudogenes or encode proteins that have been repurposed. For instance, mutant albino maize and Arabidopsis seedlings possess a defective UDP-N-acetylmuramoyl-l-alanyl-d-glutamate--2,6-diaminopimelate ligase (MurE), an intact MurE ligase being essential for peptidoglycan synthesis. In this study, we isolated a full set of cDNAs for peptidoglycan biosynthesis from P. abies. GFP fusion proteins with either P. abies (Pa)MurE or PaPBP were detected in chloroplasts. Cross-species complementation assays with PaMurE in Arabidopsis albino MurE mutants and Physcomitrium MurE chloroplast division mutants showed that the gymnosperm MurE completely rescued both mutant phenotypes. Enzymatic assay of recombinant PaMurE proteins revealed they catalyze the same reaction performed by their bacterial MurE homologs. Moreover, the expression of the PaPbp cDNA partially rescued the giant chloroplast phenotype in the moss Pbp knockout line. These results are consistent with the operation of a functional Mur gene set in the Norway spruce genome.

Peptidoglycan↗

PubMed2026

Sea nettle jellyfish venom targets proteoglycans to cause cell death and pain.

Sea nettle jellyfish cause millions of painful stings annually with little known about how their venom works and no rational treatments available. Here, we perform a systematic analysis of sea nettle venom/host interactions. The venom shows dose-dependent cytotoxic activity in human cells, and this can be blocked by dual inhibition of apoptosis and necroptosis. Using whole-genome CRISPR screening, we identified human genes and pathways that modify venom action. The top gene cluster identified regulates proteoglycan biosynthesis. We show that exogenous heparin, a drug used clinically as an anticoagulant, blocks venom cytotoxicity at a physiologically relevant dose. This effect was therapeutic, inhibiting venom even 1 hour after exposure. In vivo, heparin protected against acute spontaneous pain, thermal hyperalgesia, and mechanical allodynia induced by venom. This provides the exciting possibility of repurposing heparin, a safe, commercially available drug, as a prophylactic or therapeutic to reduce the impact of sea nettle stings.

Animals↗

PubMed2025

Evolution of antiviral host defenses against a backdrop of endogenous retroelements.

Mammalian hosts deploy a multitude of germ line-encoded mechanisms to detect and restrict virus infection. These mechanisms must avoid pathological responses to endogenous retroviruses and other endogenous retrotransposable elements (RTEs)-viruses and viruslike genomic parasites that have invaded the host germ line and are passed down the generations as host genes. Although the location, specificity, and sensitivity of innate pattern recognition receptors and restriction factors are tuned to facilitate discrimination of infecting viruses from those that are part of self, immune cross-reactions do occur. The RTE viral heritage may, therefore, compromise the ability of the host to respond to virus infection without risking pathology. Nevertheless, RTEs have the potential to be co-opted as an alarm amplification system, to be repurposed as antiviral factors, and to contribute to the evolution of antiviral genes.

Animals↗