Biology subjects

Perez, A.

Publications and source records attributed to Perez, A..

At least 19 recordsLinked to original sources

bioRxiv2026

Radiotherapy-induced vascular dysfunction alters neutrophil phenotype to promote tumor cell colonization of mammary adipose tissue

Recurrence remains a significant clinical challenge for triple-negative breast cancer patients and radiotherapy (RT) is a key therapeutic tool that significantly reduces the risk of relapse. Despite this, patients with chronic lymphopenia and a high neutrophil:lymphocyte ratio (NLR) experience recurrence at significantly higher rates than those whose hematological biomarkers return to baseline post-RT, and there are currently no treatments to prevent this relapse. Here, we utilized in vivo mouse models of lymphocyte-deficiency to identify the mechanism behind systemic immune status and recurrence. Using a model of RT-induced circulating tumor cell (CTC) colonization, we found that neutrophils are sustained in the irradiated, lymphocyte-deficient mammary tissue up to 10 days post-RT. Persistent neutrophil accumulation was accompanied by excessive vascular remodeling and tumor cell colonization of the mammary tissue, both of which were abated upon systemic neutrophil depletion. Neutrophils in the colonization-permissive microenvironment exhibited a state of pathological activation consistent with a polymorphonuclear myeloid-derived suppressor cell (PMN-MDSC) phenotype that was not seen in systemic compartments, highlighting a microenvironment-induced phenotype shift. This phenotype was recapitulated in vitro when naive neutrophils were exposed to the secretome of RT-induced senescent endothelial cells (ECs). We found that these activated neutrophils then regulated the dysfunction of irradiated ECs in a canonical NF-kB-dependent manner, increasing their barrier permeability and activating downstream inflammatory signals. Our findings not only establish neutrophils as a critical component of tumor cell colonization in lymphocyte-deficient subjects but also uncover a positive feedback loop between neutrophils and irradiated vasculature that leads to aberrant tissue remodeling and ultimately tumor cell colonization. This work deepens our understanding of how systemic factors influence treatment-damaged microenvironments, which could ultimately lead to identification of molecular targets for prevention of RT failure.

cancer biology↗

bioRxiv2026

A root pathogen drives rhizosphere enrichment of antagonistic Pseudomonas and induces production of an antimicrobial metabolite

In plants, the development of soil-borne diseases has been shown to trigger the recruitment of beneficial microbes, which contribute to defense against pathogens. However, the underlying mechanisms driving this recruitment remain elusive. Here, we used a gnotobiotic system combined with a synthetic bacterial community (SynCom) derived from the Medicago truncatula rhizosphere to dissect microbiota pathogen interaction and its role in the development of root rot caused by Aphanomyces euteiches, a devastating soilborne oomycete pathogen of legumes. Through integrated metabarcoding, metabolomics and transcriptomics, we reveal that pathogen infection restructures the bacterial SynCom, selectively enriching the microbial community with specific Pseudomonas spp. strains displaying anti A. euteiches activity. This shift alleviates root rot symptoms, triggers the biosynthesis of the antibiotic 2,4-diacetylphloroglucinol (DAPG), a Pseudomonas specialized metabolite inhibiting A. euteiches growth, and amplifies the plant endogenous isoflavonoid defense responses. Unexpectedly, we found that A. euteiches directly activates DAPG production in beneficial bacteria independently of the plant, through the production of a heat-stable, high-molecular-weight (30 - 100 kDa) extracellular components. These findings uncover a novel mechanism whereby a pathogen inadvertently activates antibiotic production in beneficial bacteria, extending the plant immune system. Our research underscores the critical role of microbial interactions in the rhizosphere in determining root disease outcomes, paving the way for microbiome-based strategies to combat root diseases.

plant biology↗

bioRxiv2026

Coral Guard substrates accelerate growth and fragment fusion for coral restoration

Coral reefs are declining globally, creating an urgent need for scalable technologies that improve the efficiency and effectiveness of active reef restoration. Coral reef restoration is increasingly constrained by algal overgrowth, which suppresses coral growth, survival, and restoration efficiency. Building on the recently developed Coral Guard platform, we evaluate its restoration performance under long-term in situ coral nursery conditions and introduce Fusion Guard Tiles, a geometry-optimized Coral Guard design that accelerates microfragment fusion. We evaluated Coral Guard Plugs using the branching coral Stylophora pistillata under complementary ex situ conditions and Fusion Guard Tiles using the massive reef-building coral Porites evermanni in in situ coral nurseries. In P. evermanni, Fusion Guard Tiles increased lateral tissue growth 2.6-fold and three-dimensional tissue surface area growth by >2.7-fold after 6 months compared with conventional substrates. After 12 months, colony height and volume were approximately 4.0-fold and 2.2-fold greater, respectively, while complete fragment fusion occurred only on Fusion Guard Tiles. In S. pistillata, Coral Guard Plugs increased lateral tissue growth by [~]1.7-fold. Microcomputed tomography revealed 10-13% higher skeletal density in both species. In P. evermanni, Fusion Guard Tiles also increased symbiont density by 70% and tissue protein content by [~]2.5-fold relative to controls. Together, these findings demonstrate that Coral Guard substrates suppress algal competition while accelerating coral growth, skeletal development, and microfragment fusion, providing a scalable, low-maintenance technology to enhance coral nursery productivity and reef restoration.

bioengineering↗

bioRxiv2026

Multi-Omics Study of Ancestry in Adults with Intracranial Cancers Glioma (MOSAIC)

BackgroundMost genomic studies of adult-type diffuse gliomas have focused on predominantly European ancestry populations, limiting the generalizability of molecular classifications and precision medicine approaches. We assembled a multi-institutional glioma cohort of diverse patients to investigate how germline ancestry, molecular subtypes, and mutational processes shape tumor biology and clinical outcomes. MethodsWe analyzed 1,102 adults with WHO 2021-classified diffuse gliomas (IDH-mutant, 1p/19q-codeleted oligodendroglioma; IDH-mutant astrocytoma; IDH-wildtype glioma) from seven U.S. institutions. Whole-exome sequencing (WES) of FFPE tumors identified somatic alterations and COSMIC SBS v3.2 mutational signatures. Genetic ancestry was estimated from WES using 1000 Genomes reference populations. Overall survival was assessed using Kaplan-Meier and multivariable models. ResultsThe cohort included 66.9% European (EUR), 21.1% Admixed American/Hispanic (AMR), 10.3% Admixed African (AFR), and 1.6% Asian (AS) ancestry. Survival followed expected molecular hierarchy (median overall survival: oligodendroglioma 15.7 years, astrocytoma 10.6 years, IDH-wildtype glioma 1.9 years). Within oligodendroglioma, AMR patients showed improved survival versus EUR (HR 0.67, 95% CI 0.48-0.94; p=0.011), with similar trends across subtypes. Somatic profiling confirmed canonical subtype-defining alterations and revealed higher ATRX alterations in AFR and AMR IDH-wildtype tumors compared with EUR. ATRX alterations were associated with improved survival only in AFR (p=0.003). Mutational signature analysis identified subtype-specific signatures, including therapy-associated signatures. Chemotherapy-related signatures were more frequent in EUR and AMR than in AFR. ConclusionsThis ancestrally diverse glioma cohort confirms established molecular classifications and identifies ancestry-associated differences in survival, somatic alterations, and mutational processes, indicating the critical need for broad representation to inform precision neuro-oncology. Key PointsO_LIA multi-institutional glioma cohort validates subtype and survival patterns across ancestries. C_LIO_LITherapy-associated mutational signatures differ by ancestry, suggesting distinct treatment-related mutational processes. C_LIO_LIAdmixed American patients show improved survival, particularly in oligodendroglioma. C_LI Importance of the StudyMost genomic studies of adult-type diffuse glioma have focused on populations of predominantly European ancestry which limits the ability to examine variation in tumor biology and clinical outcomes across populations. In this study, we assembled one of the largest ancestrally diverse cohorts of molecularly characterized adult diffuse gliomas, integrating germline ancestry inference with tumor whole-exome sequencing and mutational signature analysis. We confirm that established molecular classifications and survival hierarchies remain robust across ancestry groups. However, we also identified ancestry-associated differences in survival within specific tumor subtypes, higher ATRX alteration frequencies in African American and admixed American patients with IDH-wildtype tumors, and variation in therapy-associated mutational signatures across ancestry groups. These findings highlight the importance of incorporating population differences into genomic studies of glioma and provide a resource for future multi-ancestry investigations of glioma risk, tumor evolution, and treatment response, ultimately supporting more inclusive precision neuro-oncology.

bioinformatics↗

bioRxiv2026

A fatal plant toxicosis described more than a century ago is caused by a bacterial endophyte

Gousiekte ( quick disease) is a fatal plant toxicosis affecting livestock in South Africa. Gousiekte is characterized by the sudden death of animals following the ingestion of leaves of several species of Rubiaceae, most notably Vangueria pygmaea, Pavetta harborii, P. schumanniana and Fadogia homblei. The toxin causing gousiekte is pavettamine, a hydroxylated polyamine pavettamine for which no biosynthetic pathway is known. Interestingly, all plants known to contain pavettamine also feature obligate endophytes of the Burkholderiaceae family, in particular belonging to the Caballeronia and Paraburkholderia genera. We identified a cluster of three genes conserved in all Burkholderia s.l. endophytic symbionts of plants containing pavettamine. Constitutive expression the pavABC gene cluster in a strain of Paraburkholderia caledonica isolated from leaves of Fadogia homblei resulted in detectable levels of pavettamine in cultures, and targeted gene deletions showed the involvement of all three genes in its biosynthesis. Genomes of important animal and human pathogens of the Burkholderia pseudomallei complex encode functional homologs of the pavABC genes, indicating a potentially unrecognized role of pavettamine in disease or complications from infections. Significance statementGousiekte is a fatal disease of livestock caused by plants containing the toxin pavettamine, yet the origin of this compound has remained a mystery. We demonstrate that pavettamine is synthesized not by the plants themselves, but by their obligate bacterial endophytes via a conserved three-gene cluster, pavABC. Crucially, these genes were likely acquired via horizontal gene transfer from an ancestor of the Burkholderia pseudomallei complex, a group of significant human and animal pathogens. This discovery identifies the genetic basis of a potent toxin and suggests a previously unrecognized role for pavettamine in human infectious diseases. This work emphasizes the preeminent role of horizontal gene transfer and secondary metabolism for host-microbe interactions.

microbiology↗

bioRxiv2026

How do we align in good conversation? Investigating the link between interaction quality and multimodal interpersonal coordination

Conversations can feel effortlessly engaging or, conversely, difficult and unrewarding. Multiple factors contribute to the experienced quality and outcomes of a conversation, among them how interlocutors align with each other. The present study investigated speech-to-speech, brain-to-speech, and brain-to-brain coordination as markers of interpersonal alignment, examining their relationship with jointly perceived interaction quality and mutual affinity between conversational partners. Pairs of previously unacquainted participants (dyads) engaged in multiple short, free-form conversations on topics of varying interest while their vocal and neural activity were simultaneously recorded in a dual-EEG ("hyperscanning") setup. We analyzed interlocutors prosodic adaptation, neural speech tracking, and neural coordination during each conversation. At the speech-to-speech level, our findings reveal that partners with more positive mutual impressions became more similar in their volume and voice quality over the course of the experiment session, reflecting greater prosodic convergence. At the brain-to-speech level, we found no reliable effect of interaction quality on neural tracking of unfolding speech within any individual region, although topographical differences suggested relative modulation across scalp sites. Finally, at the brain-to-brain level, our findings show that higher perceived interaction quality enhanced inter-brain relationships across frequency bands (alpha and theta) and temporal dependencies (concurrent/near-instantaneous and recurrent/listener-lagging), with the strongest effects observed for concurrent alpha-band coupling. These findings suggest that distinct coordination processes are involved in how interlocutors experience an interaction and how they establish relational affinity, casting new light into the mechanisms that make a conversation worthwhile.

neuroscience↗

bioRxiv2026

The NMR Exchange Format (NEF): Specification and Applications

The NMR Exchange Format (NEF) is a community-driven standard for representing NMR experimental data in a consistent, interoperable, and machine-readable form. Built on the STAR syntax, NEF provides a structured framework for storing and exchanging chemical shifts, peak lists, various types of structural restraints, and related metadata, thus allowing for data exchange across software platforms. By enabling direct, lossless transfer of information, NEF simplifies multi-software workflows, improves reproducibility, and supports FAIR (Findable, Accessible, Interoperable, Reusable) data principles. We describe the NEF specification, its current implementation across commonly used NMR software packages, and its application in areas including biomolecular structure determination, metabolomics, and ligand screening. Testing demonstrates that NEF can be used to exchange complete datasets between programs without loss of information or functionality. We also outline recent developments and future directions, such as inclusion of NMR relaxation data and support for non-standard residue topologies. NEFs growing adoption highlights its potential as a unifying standard for NMR data, enabling more efficient, transparent and collaborative research.

biochemistry↗

bioRxiv2026

Efficient exploration of peptide libraries using active learning with AlphaFold-based screening

We previously showed that AlphaFold2 can be used to screen for peptide-binding epitopes targeting the extraterminal (ET) domain of Bromodomain and Extraterminal (BET) proteins from candidate protein partners identified in pull-down experiments. However, such approaches require large numbers of AlphaFold2 calculations, making exhaustive screening impractical for larger datasets, such as viral proteomes that may target the ET domain. In many cases, identifying a substantial fraction of binders--even without exhaustive coverage--would already provide valuable biological insight into these interaction networks. Here, we show that an active learning strategy based on Thompson sampling (TS) can efficiently explore peptide sequence space. Using a library derived from BRD3 pull-down experiments, TS recovers 50% of all binders using 15% of the queries required by exhaustive sampling (3.3 times improvement over random sampling). Moreover, TS consistently identifies experimentally known binding epitopes with substantially fewer queries. Because the approach relies only on binary labels, it is readily transferable to other protein-peptide systems where AF-based binding classification is applicable, as well as to peptide-property predictors for properties such as solubility or aggregation propensity.

bioinformatics↗

bioRxiv2026

Dissetangling the Vine: Phylogenomics and Historical Biogeography of Vanilla (Orchidaceae)

Renowned for its aromatic fruits and economic importance, the genus Vanilla poses longstanding taxonomic and phylogenetic challenges. Despite recent molecular studies, a comprehensive species tree is lacking, and the evolutionary processes and historical patterns shaping the genus remain poorly understood. We present a new, comprehensive phylogenomic framework for Vanilla, based on 349 low-copy nuclear genes and 76 plastid loci from the Angiosperms353 probe set, which we used to infer evolutionary relationships, assess cyto-nuclear and gene-species tree discordance, and thoroughly investigate its historical distribution and diversification. Sampling 43% of the genus, our framework resolves phylogenetic uncertainties, clarifies major clades, confirms prior hypotheses, and reveals novel placements, including V. planifolia and Vanilla subg. Gondwana. Discordances are primarily driven by incomplete lineage sorting, particularly in the vanillin-producing clade, with evidence of both ancient and recent hybridization, including a natural hybrid from the Yucatan Peninsula. Biogeographic analyses indicate a Guiana Shield origin ([~]30 Mya), Amazonia as a major diversification source, the Andes as a permeable barrier, and Central America as the main diversification sink. This study provides a robust evolutionary framework for Vanilla, supporting taxonomic revisions, comparative trait analyses, and a deeper understanding of the processes shaping this economically and biologically important orchid genus.

evolutionary biology↗

bioRxiv2026

Substrate binding and activation mechanism of the essential bacterial septal cell wall synthase FtsW

Septal peptidoglycan (sPG) synthesis in most bacteria is driven by the essential, highly conserved FtsWIOLB synthase complex, comprising the SEDS glycosyltransferase FtsW, the monofunctional transpeptidase FtsI, and the scaffolding subcomplex FtsOLB. Although apo structures of FtsWIOLB are known, no substrate-bound structures exist, likely due to the intrinsic flexibility of lipid II (L2) substrates. Here, we combined all-atom molecular dynamics simulations of E. coli FtsWIOLB with cysteine-based mutagenesis and cell-based assays to define donor and acceptor L2 binding sites in FtsW and to elucidate the complexs activation mechanism. We show that conserved arginine residues adjacent to membrane-accessible cavities in FtsW coordinate donor and acceptor L2 pyrophosphate groups, stabilizing substrate binding. The FtsWIOLB complex appears to adopt a self-inhibitory architecture in which gating elements and a periplasmic loop prevent the donor and acceptor from approaching FtsWs catalytic residue D297. Activation by FtsN or a superfission FtsW variant relieves these constraints, stabilizes acceptor-site binding, and reorients both substrates into a catalytically primed state. Long donor glycan chains further stabilize this activated conformation at the acceptor site, promoting processive sPG polymerization. Comparative modeling of ESKAPE pathogen homologs reveals conserved and divergent features of binding-site engagement and activation. We corroborate these computational findings with cysteine-based mutagenesis and crosslinking experiments. These results establish a mechanistic framework for FtsW substrate recognition and functional activation, highlighting tractable sites for structure and mechanism-based antibiotic discovery targeting SEDS-class cell wall synthases.

biophysics↗

bioRxiv2025

KCNK18 c.1107del frameshift in peripheral neuropathy links TRESK dysfunction to neuropathic pain

Neuropathic pain is commonly accompanied by hyperexcitability of nociceptive neurons, which is driven by regulation of several ion channels, including two-pore domain potassium channels (K2P) that stabilize the resting membrane potential. The TWIK-Related Spinal cord potassium channel (TRESK, K2p18.1) is predominantly expressed in sensory ganglia, where it provides major background K conductance. We describe a heterozygous c.1107del frameshift mutation in KCNK18, encoding TRESK, found in a patient with painful small fiber neuropathy and dysautonomia. This C-terminal c.1107del mutant is predicted to generate an elongated C-terminal domain, with an altered protein sequence. Whole-cell patch calmp recordings showed that the c.1107del variant reduced K current density, while heterozygous-like expression resulted in intermediate currents, consistent with a haploinsufficiency mechanism. Confocal imaging revealed decreased plasma membrane expression, indicating a trafficking-dependent loss of function while oligomerization with TRESK (homomeric channels) or TREK1 remained intact. In silico analysis revealed an altered phosphorylation pattern and reduced C-terminal hydrophobicity in the mutant TRESK. Overall, these findings support c.1107del as a pathogenic KCNK18 variant causing TRESK haploinsufficiency, offering mechanistic insight into the pathophysiology of neuropathic pain.

neuroscience↗

bioRxiv2025

Cytogenetic constraints on hybridization: A meta-analysis investigating the role of chromosome number in monocot hybrid evolution using a newly developed tool, the ploidy deviation index (PDI).

Background and aimsHybridization is a major driver of plant diversity, yet the role of cytogenetic compatibility, particularly differences in chromosome number, remains poorly understood. Differences in parental chromosome number can present barriers to hybrid formation by disrupting meiotic stability, but the extent to which biological and ecological factors influence the chromosomal architecture of hybrids remains poorly quantified, especially in monocots. This study aims to investigate how chromosome number divergence interacts with biological and ecological factors to shape hybrid formation in monocots, using a novel quantitative metric, the Ploidy Deviation Index (PDI), to standardize comparisons of hybrid cytogenetic architecture. Material and methodsWe developed and applied the PDI, a continuous index quantifying chromosome-number deviation between a hybrid and its two parents, across approximately 200 hybrid cases with documented parental karyotypes. Hybrids were categorized as homoploid, uniparentally homoploid, intermediate, or polyploid based on their PDI values. We analyzed the distribution of PDI scores in relation to type of hybrid origin (natural vs. artificial), growth habit, size of the genus (a proxy for richness), and range of chromosome number within a genus (proxy for diversity). Comparisons across categories employed Anderson-Darling k-sample tests, multinomial logistic regression, and Mann-Whitney U tests to determine significance. Key resultsHomoploid hybrids were found to be the most frequent. We found no significant difference in PDI distributions between natural and artificial hybrids. Significant variation in PDI distributions was found among growth habits, with aquatic hybrids more likely to be homoploid and geophytic hybrids showing higher proportions of polyploidy. Intermediate hybrids were common in larger genera with broader chromosome-number ranges, whereas polyploid hybrids showed the highest PDI values in large and karyotypically diverse genera. ConclusionThese results challenge long-held assumptions that polyploidy dominates hybrid formation and reveal that homoploid and intermediate chromosomal configurations are common in monocots. The PDI framework offers a powerful, standardized approach for assessing cytogenetic constraints on hybridization, with implications for systematics, evolutionary biology, and conservation.

plant biology↗

bioRxiv2025

Loop Plasticity Drives Paralog-Specific Recognition in BET ET Domains

The bromodomain and extraterminal domain (BET) family of proteins recognizes diverse peptide motifs via their conserved ET domains, yet exhibits paralog-specific binding preferences with unclear structural origins. Here, we use extensive molecular dynamics simulations and ensemble-based analyses to investigate how two known pep-tide epitope binders - one from the host regulatory protein NSD3 and one from the murine leukemia virus integrase - interact with the ET domains of BRD3 and BRD4. Our results reveal that differences in peptide recognition are not driven by large conformational changes, but by subtle variations in loop dynamics and local secondary structure. Two divergent residues (positions 35 and 36) in the flexible loop connecting helices 2 and 3 shape the conformational ensemble of each paralog by modulating the formation of flanking helices (1 and 2), which in turn control the opening of the peptide-binding cavity. These intrinsic dynamical differences influence the number and stability of accessible binding modes, with BRD3 showing greater plasticity and weaker binding, particularly for NSD3. Our findings support a model in which local sequence variation tunes conformational selection and induced fit mechanisms, offering a structural rationale for paralog-specific targeting of BET proteins. TOC Graphic O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=111 SRC="FIGDIR/small/687848v1_ufig1.gif" ALT="Figure 1"> View larger version (40K): org.highwire.dtl.DTLVardef@1215f22org.highwire.dtl.DTLVardef@1ecd6b0org.highwire.dtl.DTLVardef@2d45eorg.highwire.dtl.DTLVardef@1c473a2_HPS_FORMAT_FIGEXP M_FIG C_FIG

biophysics↗

bioRxiv2025

Extracellular matrix remodeling supports Hydra vulgaris head regeneration and stem cell invasion

The small freshwater cnidarian Hydra vulgaris is a classic model for investigating the genetic regulation of whole-body regeneration, but the underlying cell biology is comparatively underexplored. Hydra has a simple body plan consisting of two epithelial monolayers separated by an extracellular matrix (ECM). This ECM contains conserved components such as collagen and laminin, making Hydra well suited for dissecting ECM function during regeneration. Following head amputation and wound closure, we observe a retraction of ECM proteins from the wound site, creating a region of low ECM protein accumulation that persists for several days during head regeneration. Several matrix metalloproteinase (MMP) genes are expressed during this process, and MMP inhibition reduces the size of the ECM gap and results in a regenerative outcome with gross morphological defects. We further find that interstitial stem cells (ISCs), which originate in the ectoderm, localize in the regenerating head endoderm near regions of reduced ECM. This suggests that the ECM gap facilitates stem cell invasion to populate the new head with neurons and gland cells. However, inhibition of collagen cross-linking reveals that collagen synthesis is also required for regeneration, indicating that Hydra must balance ECM degradation and synthesis to complete regeneration. Together, these findings highlight ECM remodeling as a critical and conserved feature of regeneration. Summary statementThis study uses Hydra vulgaris, a highly regenerative freshwater cnidarian, to study remodeling of extracellular matrix proteins and stem cell invasion during tissue regeneration.

developmental biology↗

bioRxiv2025

Human RIG-I deficiency confers susceptibility to Kaposi Sarcoma via loss of latency control

Kaposi sarcoma (KS), caused by the DNA-virus Kaposis sarcoma-associated herpesvirus (KSHV), occurs during T cell immunosuppression (HIV, transplant) or sporadically in some immunocompetent and aging individuals (endemic, classic KS respectively). In absence of known T cell immunosuppression KS pathogenesis remains enigmatic. KS therapy with topical or oral retinoid medication, or recombinant alpha interferon, can induce remission and suggests the involvement of two signalling pathways. Retinoic acid-inducible gene-I (RIG-I) encoded by DDX58 is canonically a sensor of RNA-viruses, its function in human immunity against DNA-viruses remains poorly defined. We report a patient with classic KS, carrying a homozygous nonsense (p.Q393*) mutation in DDX58, abolishing RIG-I expression and specifically impairing RIG-I agonist responses. In isogenic cell models, loss of RIG-I compromised responses during both KSHV primary infection and viral reactivation, diminishing induction of type I interferons and interferon-stimulated genes, skewing to a persistent latent viral gene program, and dysregulating cellular pro-oncogenic pathways by transcriptomic and proteomic profiling. This work defines the first innate immunodeficiency underlying classical KS, revealing RIG-Is role in KSHV immunopathogenesis and expanding its function in human antiviral immunity beyond RNA-viruses, while identifying promising therapeutic targets. Significance statementRIG-I deficiency causes classic KS by failing to control KSHV infection and reactivation, expanding its role beyond RNA-viruses.

immunology↗

bioRxiv2025

Reducing Honey Bee Winter Mortality with Molybdenum Supplementation: Field Evidence Across Europe

Nutrition is key to improve honey bees resilience to environmental stress factors that threaten their health. Yet, little is known about the micronutritional needs of colonies, in particular about molybdenum, an essential trace element in biology. This study focuses on a coordination complex based on molybdenum Mo(+V) which was assessed for compatibility with standard beekeeping practices. It was found to be non-toxic for bees, stable and easy to use. Importantly, it does not leave any residues in honey produced. This study investigated how supplementation with few milligrams of this complex can improve hive performance at early spring and reduce winter mortality. Over a two-year field campaign, 283 beehives spread over 6 apiaries located in Spain, Greece and France were involved: 142 beehives supplemented with the molybdenum-based compound and 141 beehives as a control group. Supplementation resulted in a significant reduction in winter colony losses, averaging a 44% decrease, ranging between 27% and 75% in the different apiaries. The risk of death was twice lower in the Na-Mo2O4-EDTA group compared to the control group (risk ratio: 0.51). The impact on bee populations and honey production was also evaluated. A significant increase in honey reserves within the brood area of 107% was observed in the Greek apiary, whereas no comparable effect was detected in Spain, suggesting that local environmental conditions or management practices may influence this parameter. This study highlights the importance of molybdenum in the management of honey bees as an efficient tool to reduce the winter mortality of the colonies. HighlightsO_LIMolybdenum-based feed supplementation reduced honey bee winter mortality by 44% in average and up to 75% C_LIO_LIThere are no adverse effects on honey bee health or honey and wax composition. C_LIO_LISupplement showed variable effects on honey reserves and no effects on bee population. C_LIO_LIALP levels increased transiently, while the TAC was unaffected.Supplementation with Molybdenum-based compound represents a promising strategy to enhance colony overwintering success C_LI

zoology↗

bioRxiv2025

APOE genotype and sex drive microbiome divergence after microbiome standardization in APOE-humanized mice

The APOE4 allele is the greatest known genetic factor for sporadic or late onset Alzheimers Disease (LOAD). Gut microbiome (GMB) dysbiosis can lead to poorer outcomes in disease. The intersection of sex, APOE genotype, inflammation, and gut microbiota is incompletely understood. Previous studies in humans and humanized APOE mice have demonstrated APOE-genotype specific differences in the GMB. However, most of these studies were unable to resolve bacteria to the species level. It remains unclear how GMB changes with age and sex in the context of APOE genotype. In this study, humanized male mice with either APOE 2, 3, or 4 genotype were bred with the same two C57BL/6J sisters to standardize microbiomes across lines and monitor divergence based on APOE allele. Stool samples were collected at breeder set up and from the heterozygous (F1) and homozygous (F2) generations at wean and 6 months old. Stool was assessed via shallow shotgun sequencing to enable species and strain level taxonomic resolution. The heterozygous pups microbiome resembled each other at wean across all genotypes. However, the heterozygous pups, and their homozygous offspring continued to diverge, particularly the APOE2 females. In homozygous mice, the GMB demonstrated significance divergence at 6 months of age based on sex and APOE genotype. In comparison to their APOE3 and APOE4 counterparts, APOE2 females and males demonstrated an increased quantity of bacteria associated with anti-inflammatory profiles, including in the Lachnospiraceae family (Lachnospiraceae bacterium UBA3401) and decreased quantities in the Turicibacteraceae family (higher levels are associated with LOAD). ImportanceThe APOE4 allele is implicated as a significant risk factor for many diseases including cardiovascular disease (responsible for more deaths than any other disease) and sporadic or late onset Alzheimers Disease (accounts for an estimated 60% to 80% of all dementia cases). It is known that the gut microbiome (GMB) is affected by different genotypes and disease states. Mouse model studies have environmental and genetic controls allowing a specific gene to be studied. This study aims at discovering key GMB species differences allowing for future therapeutic targets. The GMB of the experimental mice was standardized and genotype and sex-specific divergence was observed with species and even strain level taxonomic resolution. Reported here are the first data demonstrating GMB divergence over time driven by APOE genotype from an inherited source and the first data to identify APOE genotype-specific bacteria species that may serve as therapeutic targets in APOE-driven disease.

microbiology↗

bioRxiv2025

Expanding the Orchidaceae Virome Through Analysis of Public-Domain Sequencing Data

Orchidaceae is one of the largest plant families, renowned for its ornamental appeal, uses in food, cosmetics, and medicine, and its vital importance in ecosystem health and biodiversity. However, despite their diversity and economic significance, knowledge about the viruses associated with orchid species remains limited. Fortunately, the widespread adoption of high-throughput sequencing enables the collection of indirect information about the viruses associated with various plant hosts. In this work, we conducted an integrated data analysis of viruses associated with Orchidaceae by reexamining 2,789 public RNA-seq datasets encompassing 41 genera, 18 subtribes, and five subfamilies. We identified sequences associated with 163 viruses, 13 representing new associations with Orchidaceae. Additionally, 117 sequences likely represent putative novel species, including six tentative new genera within Benyviridae, Betaflexiviridae, Phenuiviridae, and Tymoviridae. Analysis of the updated Orchidaceae virome revealed a strong correlation between the pairs Alphaflexiviridae/Virgaviridae, Rhabdoviridae/Partitiviridae, and Partitiviridae/Secoviridae and a negative correlation between Alphaflexiviridae/Partitiviridae; Virgaviridae/Partitiviridae; Rhabdoviridae/Alphaflexiviridae; Betaflexiviridae/Alphaflexiviridae; and Secoviridae/Alphaflexiviridae in addition to correlations between virus genera and orchid lifestyles. A network analysis of the host range of orchid viruses was also performed in addition to a preliminary estimate of the size of the Orchidaceae virome. IMPORTANCEDespite their diversity, little is known about viruses associated with orchids. Plant viruses significantly threaten agriculture and may harm orchid conservation. Without detailed characterization of the orchid virome and suitable diagnostic tools, viruses could unintentionally enter ecosystems and cultivation fields from contaminated sources. Sequence information is crucial for developing detection tests for quick virus identification, supporting disease management strategies, and producing virus-free plants. In addition, understanding ecological factors contributing to virus transmission--like primary infection sources, vectors, and alternative hosts--is essential for selecting control measures to prevent viral diseases and manage outbreaks. Data mining provides a cost-effective method to bridge knowledge gaps, highlight trends that are useful for plant virus surveillance, and inform epidemiological decisions. The analysis presented here offers a global perspective on the Orchidaceae virome that could guide future research and virus vigilance programs and enhance our understanding of plant virus diversity.

bioinformatics↗