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Andrew, C.

Publications and source records attributed to Andrew, C..

3 recordsLinked to original sources

Evasion of Hepatic ILC1 Immunosurveillance Drives Breast Cancer Liver Metastasis

Metastasis, the dissemination of cancer cells to distant organs, is an inefficient process1, yet remains the leading cause of cancer-related mortality2. The cellular barriers and evasion mechanisms governing organ-specific susceptibility remain incompletely understood3-5, hindering the development of effective anti-metastatic therapies6. Here, we show that liver-resident type 1 innate lymphoid cells (ILC1s) constitute an essential immunosurveillance barrier against breast cancer liver metastasis that can be bypassed through either cancer cell intrinsic or host-dependent mechanisms. In a multi-organ metastatic breast cancer patient cohort, liver metastasis occurred later and was associated with poorer survival than lung metastasis, with elevated body mass index emerging as a clinical risk factor. This metabolic vulnerability was recapitulated in mice, where a high-fat diet induced hepatosteatosis and selectively enhanced breast cancer colonization of the liver. Mechanistically, liver and lung colonization were restrained by ILC1s and circulating natural killer (NK) cells, respectively. Following cancer cell challenge, NK cells expanded and activated, employing lytic granule pathways and the death receptor DR5 for clearance, whereas activated ILC1s selectively required high DR5 expression on cancer cells, supported by AP-2a (TFAP2A) mediated transcriptional activation, for effective immunosurveillance. Heterozygous copy number deletion at TNFRSF10B (encoding DR5) in human tumours reduced DR5 expression and predisposed to liver metastasis. Hepatosteatosis further compromised this barrier by reducing IL-15 expression in macrophages, thereby depleting hepatic ILC1s effects reversible with glucagon-like peptide-1 (GLP-1) receptor agonists. Thus, hepatic ILC1s form a critical organ-specific barrier to breast cancer metastasis, vulnerable to both cancer cell-intrinsic DR5 downregulation and host metabolic dysfunction.

immunology↗

Regulation of pitcher fluid volume and properties in six ecologically distinct Bornean Nepenthes species

Carnivorous Nepenthes plants capture and digest prey in fluid-filled pitchers, whose fluid level is subject to fluctuations caused by rain and evaporation. It was found that N. rafflesiana pitchers can reduce these fluctuations by regulating their fluid volume and composition. Here, we investigate whether and to what extent this ability occurs in other Nepenthes species varying in morphology, trapping mechanisms, habitat, lifespan and nutrient sources. We hypothesised that species more exposed to fluid level fluctuations or relying more on fluid for prey capture would exhibit more intensive regulation. In six Bornean Nepenthes species, we quantified the effect of pitcher fluid level on prey-capture efficiency, the natural fluctuations in fluid volume, and the plants response to manipulations of the fluids volume, concentration and pH. The prey capture of Nepenthes species depended to varying degrees on the pitcher fluid level: in species with waxy inner walls, capture efficiency decreased at high fluid levels, as prey could escape easily. In contrast, species with wax-free walls and steep peristomes retained prey efficiently, regardless of fluid level. Although all Nepenthes species were able to secrete and absorb water and electrolytes, the regulation rate varied considerably. The rates of the various secretion and absorption processes (concentration/volume-dependent rates of electrolyte/water transport) were positively correlated with one another, suggesting that they all depend on the activity of the pitcher glandular epithelium. While differences and similarities in fluid regulation may be partly due to phylogeny, the observed species differences can also be explained by the pitchers trapping mechanisms and ecological factors. We found weaker regulation in Nepenthes species growing in sheltered understorey habitats, and in species utilising alternative nutrient sources, which may reduce their reliance on pitcher fluid. Our study highlights the diversity of ecological strategies in pitcher plants and demonstrates how these are influenced by environmental conditions. Lay SummaryNepenthes pitcher plants have fluid-filled pitchers to capture and digest prey. Can they control the volume and composition of their fluids? We found that all six species studied regulated their fluids, but to varying degrees. Species differences can be explained by the plants habitat, pitcher morphology and nutrient acquisition strategies.

Plant Biology↗

MycorrhizaTracer: A BIOINFORMATIC PIPELINE FOR FUNGI AND PLANT CLASSIFICATION OF SANGER DNA SEQUENCES

Processing Sanger DNA sequences remains a routine yet technically demanding step in many biodiversity and ecological studies, particularly when barcoding large numbers of environmental samples. Manual inspection and editing of trace files, DNA sequence alignment, and classification using taxonomic reference databases is time-consuming, inconsistent, and prone to error. These challenges are compounded in studies involving degraded samples, in-house DNA sequencing, under-described taxa, or when investigators have limited access to computational tools. We present MycorrhizaTracer, an open-source, fully automated pipeline for processing and taxonomically classifying large batches of Sanger sequencing chromatograms. We have optimized it for fungal and plant taxa, but it is adaptable across the tree of life. The pipeline performs quality trimming, consensus generation from bidirectional reads, taxonomic classification via BLAST, clustering, optional salvaging of low-quality sequences, and functional annotation of fungal taxa. Designed for scalability and ease of use, MycorrhizaTracer can process thousands of DNA chromatograms in a matter of hours without the need for an HPC. Accuracy and ecological relevance are ensured by features such as gene region-specific taxonomic filtering and sequence-based clustering of unclassified reads. By streamlining trace-to-taxon workflows, MycorrhizaTracer reduces the burden of manual curation, supports reproducibility, and enables efficient recovery of biodiversity data from Sanger sequences - particularly in field-based or resource-limited research contexts.

bioinformatics↗