Biology subjects

Holman, L.

Publications and source records attributed to Holman, L..

8 recordsLinked to original sources

bioRxiv2026

SedaDNA metabarcoding reveals hidden histories of within-species sequence variation

Most genetic data come from contemporary populations, leaving historical changes in within-species variation poorly documented. Sedimentary ancient DNA (sedaDNA) offers an opportunity to recover historical sequence variation, but its potential to reconstruct temporal changes in within-species composition remains underexplored. Here, we analysed dated sediment cores from eight Atlantic and Mediterranean coastal wetlands using COI and 18S metabarcoding, treating amplicon sequence variants as putative haplotypes. Across native, non-indigenous and cryptogenic taxa, accumulated haplotype diversity and geographic sharing varied markedly among species and markers, without consistently distinguishing species status. Temporal reconstructions revealed that accumulated haplotype networks combined distinct sets of variants detected across historical periods. Broader analyses of 18S data further showed substantial variation in haplotype composition among periods, sites and taxa. By resolving the temporal and spatial distributions of within-species sequence variants, our findings demonstrate how sedimentary DNA archives can uncover historical dimensions of biodiversity obscured by time-aggregated analyses, establishing a foundation for historical metaphylogeography.

evolutionary biology↗

bioRxiv2026

Long-term biodiversity responses to anthropogenic change are spatially and taxonomically heterogeneous across coastal wetlands

Coastal wetlands have undergone centuries of anthropogenic modification, yet their long-term biodiversity trajectories remain poorly understood because ecological monitoring rarely extends beyond recent decades. Sedimentary ancient DNA (sedaDNA) offers a historical perspective for evaluating how biodiversity patterns vary across environmental contexts and timescales. We combined COI and 18S sedaDNA metabarcoding with 210Pb and radiocarbon chronologies, sediment geochemistry and stable-isotope records from eight coastal wetlands across four regions of the Iberian Peninsula. We reconstructed changes in eukaryotic amplicon sequence variant (ASV) richness and taxonomic composition and examined their relationships with an Anthropogenic Enrichment Index (AEI) based on ten elements potentially associated with human activities. Richness-AEI relationships differed among sediment records and genetic markers. Higher enrichment was associated with lower richness for both markers in one Cadiz record, whereas COI richness increased with enrichment in the Ebro Delta. However, after accounting for calendar time, only the positive association in the Ebro Delta remained statistically significant, indicating that several initial relationships were partly explained by shared temporal trends. Exploratory rolling correlations further suggested that the direction of richness-enrichment associations varied across historical periods within individual records. Taxonomic profiles differed between markers and wetlands, while community composition was strongly differentiated among sediment records, highlighting ecological variation not captured by richness alone. Multiproxy changes also followed locally specific configurations rather than a common regional trajectory. Together, these findings show that long-term relationships between sedimentary enrichment and biodiversity are context-dependent and sensitive to the temporal perspective considered. Integrating molecular, geochemical and isotopic records can therefore improve the historical interpretation of biodiversity change and inform conservation approaches that account for taxonomic composition, environmental history and locally appropriate reference conditions.

ecology↗

bioRxiv2026

AI-ASSISTED NANOMEDICINE REVEALS SYSTEMIC IMMUNE IMPACT IN OVARIAN CANCER METASTASIS

Ovarian cancer, a gynecological malignancy, poses a significant challenge as researchers struggle to comprehend how tumor cells communicate with the immune system. Ovarian tumors contain both bulk cancer cells and cancer stem cells (CSCs), which are linked to chemoresistance, relapse, and immune escape. However, it remains unclear whether these two populations affect immune cells differently. To investigate this, a study used surface-enhanced Raman spectroscopy (SERS) combined with machine learning to examine the biochemical changes in peripheral blood mononuclear cells (PBMCs) after co-culture with OVCAR4 ovarian cancer cells or OVCAR4-derived CSC-enriched populations. PBMCs and tumor cells were co-cultured for 48 hours in an indirect Transwell system, allowing exchange of soluble factors without direct cell contact. SERS spectra were acquired on gold-coated nickel substrates and analyzed using principal component analysis, t-test, and a linear support vector machine (SVM). The results showed that PBMCs co-cultured with CSCs and PBMCs co-cultured with OVCAR4 cells exhibited distinct spectral profiles. Moreover, the SVM demonstrated a high cross-validated accuracy of 98.9% in separating these two populations. PBMCs exposed to CSCs exhibited higher adenine and carbohydrate signals, while those exposed to OVCAR4 cells displayed higher protein and lipid signals. Interestingly, the tumor cells themselves exhibited the same pattern at baseline. Moreover, six out of the ten most discriminating bands were shared between the tumor and PBMC comparisons, indicating a consistent direction of change. These findings suggest that tumor-derived soluble factors leave a distinct biochemical signature on PBMCs. Label-free SERS combined with machine learning offers a sensitive approach for studying tumor-immune communication and developing blood-based tools to monitor ovarian cancer.

cancer biology↗

bioRxiv2026

Synthetic Immunological Niche Reveals Early Immune Dysregulationand Stratifies Therapeutic Response in Type 1 Diabetes

In Type 1 Diabetes (T1D), disease onset and response to immunotherapy vary widely among individuals, reflecting heterogeneous stage-specific immune dysregulation that remains undefined. To investigate this heterogeneity, we engineered a microporous polycaprolactone scaffold that forms a synthetic immunological niche (IN) upon subcutaneous implantation, enabling in vivo capture of systemic immune dysregulation. In non-obese diabetic (NOD) mice, longitudinal transcriptomic profiling of IN-infiltrating cells identified early-stage genes relatively enriched for myeloid cells, followed by progressive increases in T cell-associated dysregulation at later stages that distinguished T1D progressors from non-progressors. We derived an early-stage IN-based T1D gene signature capturing immune alterations. The signature stratified NOD progressors from non-progressors as early as 6 weeks of age and was conserved across human T1D datasets, distinguishing T1D from non-diabetic individuals in spleen and pancreatic lymph node samples, but not peripheral blood. Signature-based stratification further revealed enrichment of macrophage-associated TNF- pathways in NOD progressors, validated in human T1D islets. Given heterogeneous response to anti-TNF- therapy, IN profiling identified resistance-associated mechanisms and enabled derivation of a pathway score that prospectively distinguished treatment-sensitive from resistant mice prior to therapy, establishing the IN as a minimally invasive platform for detecting stage-wise immune dysregulation and stratifying immunotherapy response in T1D.

bioengineering↗

bioRxiv2021

Polygenic signals of sexually antagonistic selection in contemporary human genomes

Sex differences in the fitness effects of genetic variants can influence the rate of adaptation and the maintenance of genetic variation. For example, "sexually antagonistic" (SA) variants, which are beneficial for one sex and harmful for the other, can both constrain adaptation and increase genetic variability for fitness components such as survival, fertility, and disease susceptibility. However, detecting variants with sex-differential fitness effects is difficult, requiring genome sequences and fitness measurements from large numbers of individuals. Here, we develop new theory for studying sex-differential selection across a complete life cycle, and test our models with genotypic and reproductive success data from ~250,000 UK Biobank individuals. We uncover polygenic signals of sex-differential selection affecting survival, reproductive success and overall fitness, with signals of sex-differential reproductive selection reflecting a combination of SA polymorphisms and sexually concordant polymorphisms in which the strength of selection differs between the sexes. Moreover, these signals hold up to rigorous controls that minimise the contributions of potential confounders, including sequence mapping errors, population structure, and ascertainment bias. Functional analyses reveal that sex-differentiated sites are enriched in phenotype-altering genomic regions, including coding regions and loci affecting a range of quantitative traits. Population genetic analyses show that sex-differentiated sites exhibit evolutionary histories dominated by genetic drift and/or transient balancing selection, but not long-term balancing selection, which is consistent with theoretical predictions of effectively weak SA balancing selection in historically small populations. Overall, our results are consistent with polygenic sex-differential--including SA--selection in humans. Evidence for sex-differential selection is particularly strong for variants affecting reproductive success, in which the potential contributions of non-random sampling to statistical signals of sex-differentiation can be excluded.

evolutionary biology↗

bioRxiv2021

Sexual selection affects the evolution of physiological and life history traits

Sexual selection and sexual conflict are expected to affect all aspects of the phenotype, not only traits that are directly involved in reproduction. Here, we show coordinated evolution of multiple physiological and life history traits in response to long-term experimental manipulation of the mating system in populations of Drosophila pseudoobscura. Development time was extended under polyandry relative to monogamy in both sexes, potentially due to higher investment in traits linked to sexual selection and sexual conflict. Individuals (especially males) evolving under polyandry had higher metabolic rates and locomotor activity than those evolving under monogamy. Polyandry individuals also invested more in metabolites associated with increased endurance capacity and efficient energy metabolism and regulation, namely lipid and glycogen. Finally, polyandry males were less desiccation- and starvation-resistant than monogamy males, suggesting trade-offs between resistance and sexually selected traits. Our results provide experimental evidence that mating systems can impose selection that influences the evolution of non-sexual phenotypes such as development, activity, metabolism, and nutrient homeostasis.

evolutionary biology↗

bioRxiv2020

Social immunity and chemical communication in the honeybee: immune-challenged bees enter enforced or self-imposed exile

Animals living in large colonies are especially vulnerable to infectious pathogens, and may there-fore have evolved additional defences. Eusocial insects supplement their physiological immune systems with social immunity, a set of adaptations that impedes the entrance, establishment, and spread of pathogens in the colony. We here find that honey bee workers (Apis mellifera) that had been experimentally immune-challenged with lipopolysaccharide (LPS) often exited the hive and subsequently died; some individuals were dragged out by other workers, while others appeared to leave voluntarily. In a second experiment, we found that healthy workers treated with surface chemicals from LPS-treated bees were evicted from the hive more often than controls, indicating that immune-challenged bees produce chemical cues or signals that elicit their eviction. Thirdly, we observed pairs of bees in the lab, and found that pairs spent more time apart when one member of the pair had received LPS, relative to controls. Our findings suggest that immune-challenged bees altruistically banish themselves, and that workers evict sick individuals which they identify using olfactory cues, putatively because of (kin) selection to limit the spread of pathogens within colonies.

animal behavior and cognition↗

bioRxiv2018

Researchers preferentially collaborate with same-gendered colleagues across the life sciences

Evidence suggests that women in academia are hindered by conscious and unconscious biases, and often feel excluded from formal and informal opportunities for research collaboration. In addition to ensuring fairness and helping to redress gender imbalance in the academic workforce, increasing womens access to collaboration could help scientific progress by drawing on more of the available human capital. Here, we test whether researchers tend to collaborate with same-gendered colleagues, using more stringent methods and a larger dataset than in past work. Our results reaffirm that researchers co-publish with colleagues of the same gender more often than expected by chance, and show that this gender homophily is slightly stronger today than it was 10 years ago. Contrary to our expectations, we found no evidence that homophily is driven mostly by senior academics, and no evidence that homophily is stronger in fields where women are in the minority. Interestingly, journals with a high impact factor for their discipline tended to have comparatively low homophily, as predicted if mixed-gender teams produce better research. We discuss some potential causes of gender homophily in science.

scientific communication and education↗