Biology subjects

Marcu, D.

Publications and source records attributed to Marcu, D..

4 recordsLinked to original sources

bioRxiv2026

Dietary fibre responses emerge through host-dietary regime interplay: Apple pectin modulates immune reactivity in adult zebrafish

Dietary fibres are rarely consumed independently. Instead, they form part of an overall diet that includes dietary fibres from different sources, in varying amounts and consumed under different feeding patterns. Here, we tested how dietary regimes containing apple pectin, oat {beta}-glucan, or cellulose shaped the host. We analysed gut microbiome composition by 16S rRNA sequencing, measured brain and intestinal SCFA profiles by targeted metabolomics, and assessed immunomodulation by measuring gene expression systemically in the blood and locally in the spleen, as well as intestinal enzyme activity. The dietary intervention was conducted for 12 weeks on adult female and male zebrafish (Danio rerio). Our results show that the gut microbial composition can be relatively stable across different dietary fibre exposure patterns yet still vary significantly between the sexes. Additionally, the effect of sex on the gut microbiome may become more evident when dietary fibres are administered at high dosages, but intermittently. Dietary fibre regimes can alter intestinal short-chain fatty acid profiles more readily than brain profiles, which show a stronger sexually dimorphic response. Interestingly, apple pectin modulated the zebrafish immune response through interactions dependent on the overall regime, tissue, sex, and host immune status. Notably, tissue il1b gene expression differed depending on how apple pectin was administered and the host's physiological state. Collectively, our study emphasises the highly context-specific effects of dietary fibres, shaped by the dynamic interplay between the overall dietary regime and intertwined host factors.

systems biology↗

bioRxiv2025

Microbiota/gut/neuron axis promotes Drosophila ageing via Acetobacter, Tachykinin, and TkR99D

Gut microbiota exert an evolutionarily conserved influence on ageing, from invertebrates to humans. How do microbes that are physically confined to the gut lumen affect the systemic physiological process of ageing? In female Drosophila, we show that microbiota increase expression of the peptide hormone Tachykinin (Tk), which corresponds to reduced lifespan. Tk is required for microbiota to shorten lifespan, with knockdown rendering flies constitutively long-lived even in the presence of an intact microbiota. This lifespan extension does not come with canonical costs to fecundity or feeding, but impacts on triacylglyceride (TAG) storage suggest adaptive functions in metabolic homeostasis. In flies with defined (gnotobiotic) microbiotas, we show that we can model Tk-dependent effects of microbiota on lifespan and TAG by monoassociation with Acetobacter pomorum. These effects require Tk in the midgut, and the cognate TK receptor TkR99D in neurons, implicating a microbiota-gut-neuron relay. This relay also appears to compromise gut barrier function in aged flies, indicating roles in healthspan as well as lifespan. However, the effect of TkR99D is independent of its reported role in insulin signalling and adipokinetic hormone signalling which, respectively, are canonical regulators of lifespan and TAG metabolism, suggesting a non-canonical role for TkR99D elsewhere in the nervous system. Altogether our results implicate a microbiota-gut-neuron axis in ageing, via a specific bacterium modulating activity of a specific and evolutionarily-conserved hormone.

genetics↗

bioRxiv2024

Within-ejaculate haploid selection reduces disease biomarkers in human sperm

The germline is widely regarded as a checkpoint against the inheritance of damaged genomes, yet the mechanisms that could enact such filtering remain poorly resolved. Of the millions of sperm in a human ejaculate, only one fertilises the egg, creating a strong opportunity for selection among gametes. Combining within-ejaculate selection on sperm quality with whole-genome sequencing and proteomics in healthy donors, we find that this selection is biased against molecular signatures of age-related disease. The most reproducibly diverging genes are tumour suppressors, and genes diverging under sperm longevity-based selection are enriched for senescence-associated genes involved in genome maintenance and oxidative stress response. High-quality sperm are further depleted of inflammation- and cancer-associated proteins. This genomic signature is conserved in zebrafish, in which longer-lived sperm sire longer-lived offspring. We propose that within-ejaculate selection acts as a pre-fertilisation filter against age-related disease alleles, with implications for offspring lifespan and healthspan.

molecular biology↗

bioRxiv2020

NERO: A Biomedical Named-entity (Recognition) Ontology with a Large, Annotated Corpus Reveals Meaningful Associations Through Text Embedding

Machine reading is essential for unlocking valuable knowledge contained in the millions of existing biomedical documents. Over the last two decades 1,2, the most dramatic advances in machine-reading have followed in the wake of critical corpus development3. Large, well-annotated corpora have been associated with punctuated advances in machine reading methodology and automated knowledge extraction systems in the same way that ImageNet 4 was fundamental for developing machine vision techniques. This study contributes six components to an advanced, named-entity analysis tool for biomedicine: (a) a new, Named-Entity Recognition Ontology (NERO) developed specifically for describing entities in biomedical texts, which accounts for diverse levels of ambiguity, bridging the scientific sublanguages of molecular biology, genetics, biochemistry, and medicine; (b) detailed guidelines for human experts annotating hundreds of named-entity classes; (c) pictographs for all named entities, to simplify the burden of annotation for curators; (d) an original, annotated corpus comprising 35,865 sentences, which encapsulate 190,679 named entities and 43,438 events connecting two or more entities; (e) validated, off-the-shelf, named-entity recognition automated extraction, and; (f) embedding models that demonstrate the promise of biomedical associations embedded within this corpus.

systems biology↗