Biology subjects

Wood, W.

Publications and source records attributed to Wood, W..

5 recordsLinked to original sources

bioRxiv2026

Intestinal bacteria hijack an evolutionarily conserved epithelial repair signal

Apoptosis in the gut triggers an expansion in the Enterobacteriaceae family of bacteria, causing both prolonged tissue injury and delayed repair. However, the mechanisms linking the Enterobacteriaceae bloom and subsequent deleterious tissue response are relatively unknown. Here, we establish purines as a major component of the apoptotic secretome that are consumed by bacteria. Explicitly, we identify hypoxanthine as a critical metabolite that is taken up and metabolised by both pathogenic and commensal species within the Enterobacteriaceae family. Epithelial cells release hypoxanthine into the extracellular space during early stages of apoptosis via the upregulation of equilibrative nucleoside transporters 1/2 (ENT1/2). Critically, beyond simply linking host and microbe, we delineate a connection between the release of hypoxanthine from the dying cell and the ability of the host to repair damaged epithelial tissue. Hypoxanthine is a potent promoter of epithelial cell repair in both gut and skin across the phylogenetic tree including humans, mice, zebrafish, and fruit flies and promotes similar ATP production and cellular proliferation in eukaryotic and microbial recipients. Thus, the preferential utilisation of hypoxanthine by the Enterobacteriaceae directly competes with the host for a core reparative signal.

microbiology↗

bioRxiv2026

No adaptive plasticity in the heat tolerance of lizard sperm

O_LIAdaptive phenotypic plasticity can help organisms cope with global warming by increasing their heat tolerance, yet most research has focused on whole-organism traits. Much less is known about thermal plasticity at the gamete level despite increasing evidence that reproduction, and particularly sperm function, is especially sensitive to heat. C_LIO_LIWe tested for plasticity in sperm heat tolerance in two ways: via male thermal acclimation (pre-ejaculate stage) and via sperm cell heat hardening (post-ejaculate stage) in brown anole lizards (Anolis sagrei). We also measured plasticity in several other sperm and ejaculate traits in response to male thermal acclimation. C_LIO_LITo test for effects of male thermal acclimation, adult males were exposed to one of two ecologically realistic, fluctuating temperature regimes that either mimic cool spring conditions or projected future summer conditions for eight weeks. Throughout this period, we repeatedly measured sperm heat tolerance (LT50), baseline motility, and sperm count. We also measured sperm morphology at the end of thermal acclimation. We predicted that males in the warmer treatment would produce more heat tolerant sperm. C_LIO_LITo test for post-ejaculate heat hardening, we compared the heat tolerance of ejaculated sperm that either did or did not experience a high but non-lethal temperature prior to heat tolerance measurement. C_LIO_LIWe found no plasticity in sperm heat tolerance due to either male thermal acclimation or sperm cell heat shock. Long-term thermal acclimation of males did not increase sperm heat tolerance, nor change motility, sperm count, or sperm morphology. We also found no evidence for post-ejaculate heat hardening, as exposing sperm cells to mild sublethal heat shock did not enhance sperm heat tolerance. C_LIO_LIOur results indicate that gametic traits have limited capacity for plastic adjustment to thermal stress, which is broadly consistent with the low levels of thermal plasticity found for whole-organism thermal tolerance across ectotherms. This highlights the vulnerability of reproductive traits to rising temperatures and the importance of evolutionary and behavioral responses to buffer organisms from climate change. C_LI

ecology↗

bioRxiv2026

Nuclear plasticity regulates macrophage phagocytic capacity in vivo

Macrophages fine-tune their appetite to fulfil their clearance role, but how they achieve this is incompletely understood. The nucleus can sense and respond to extracellular physical challenges, but whether it can also detect and react to intracellular mechanical inputs is unclear. Here, we tested the hypothesis that phagosomes exert a strain on the nucleus, and that the consequent nuclear mechanoresponse influences macrophage appetite. Combining genetic manipulation and live in vivo imaging, we show that engulfed apoptotic bodies indent the nucleus of Drosophila embryonic macrophages, leading to nuclear deformation and causing an increase in Lamin B levels. We demonstrate that these phagosome-induced nuclear molecular and mechanical adaptations are critical for macrophages to sustain uptake - unveiling a role for nuclear plasticity in the regulation of macrophage phagocytic capacity in vivo.

cell biology↗

bioRxiv2023

Imaging membrane damage in ferroptosis and necrosis by wash-free fluorogenic chemical probes

Selectively labelling cells with damaged membranes is needed in contexts as simple as identifying dead cells in culture, or as complex as imaging membrane barrier functionality in vivo. The commonly used dyes are permanently coloured/fluorescent dyes that are simply excluded by intact membranes, but to achieve good image contrast therefore requires removing their extracellular signal by washing or background subtraction, which are not possible in vivo. Here, we develop fluorogenic probes which sensitively and selectively reveal damaged cells, without needing washing steps since their fluorescence turns on from near-zero background. From a set of novel fluorogenic probes impermeabilised by sulfonations along different vectors, we identify a specific disulfonated fluorogenic scaffold that enters cells only upon membrane damage, where it is enzymatically activated to mark them. The esterase probe iPS-FS2 is a reliable tool to reveal live cells that have been permeabilised by biological, biochemical, or physical membrane damage; and it can be used in multicolour microscopy. We confirm the modularity of this approach by also adapting it for redox-unmasked cell-excluded probes with improved hydrolytic stability. This scaffold-based design thus provides tools for wash-free in vivo imaging of membrane damage, which is relevant across many pathologies. The insightss gained from these probes should also be translatable to damage-targeted prodrugs, for selective therapy of membrane-compromised cells. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=145 SRC="FIGDIR/small/543437v1_ufig1.gif" ALT="Figure 1"> View larger version (53K): org.highwire.dtl.DTLVardef@1594016org.highwire.dtl.DTLVardef@7e7053org.highwire.dtl.DTLVardef@1008cb0org.highwire.dtl.DTLVardef@1148bd7_HPS_FORMAT_FIGEXP M_FIG C_FIG

molecular biology↗

bioRxiv2023

Epigenetic signature of human immune aging: the GESTALT study.

Age-associated DNA methylation in blood cells convey information on health status. However, the mechanisms that drive these changes in circulating cells and their relationships to gene regulation are unknown. We identified age-associated DNA methylation sites in six purified blood borne immune cell types (naive B, naive CD4+and CD8+ T cells, granulocytes, monocytes and NK cells) collected from healthy individuals interspersed over a wide age range. Of the thousand of age-associated sites, only 350 sites were differentially methylated in the same direction in all cell types and validated in an independent longitudinal cohort. Genes close to age-associated hypomethylated sites were enriched for collagen biosynthesis and complement cascade pathways, while genes close to hypermethylated sites mapped to neuronal pathways. In-silico analyses showed that in most cell types, the age-associated hypo- and hypermethylated sites were enriched for ARNT (HIF1{beta}) and REST transcription factor motifs respectively, which are both master regulators of hypoxia response. To conclude, despite spatial heterogeneity, there is a commonality in the putative regulatory role with respect to transcription factor motifs and histone modifications at and around these sites. These features suggest that DNA methylation changes in healthy aging may be adaptive responses to fluctuations of oxygen availability.

molecular biology↗