Biology subjects

Robson, T.

Publications and source records attributed to Robson, T..

4 recordsLinked to original sources

bioRxiv2026

PEATREST: A lifecycle assessment (LCA) model of carbon fluxes for restored afforested peatlands

Peatlands are an important terrestrial carbon sink which, when drained, can produce substantial CO2 efflux. Low productivity forestry planted on drained peatlands can become a net carbon source if losses from drained soils exceed sequestration by the trees. Decision support tools which assist resource allocation and intervention planning in forest-to-bog restoration are needed to mediate this substantial environmental harm. Predicting carbon mitigation benefits associated with forest-to-bog restoration is a major challenge, however, due to the lack of long-term monitoring programs and the fact that mitigation times depend on processes distant from the intervention. Here we introduce the PEATREST life cycle assessment (LCA) which predicts carbon fluxes associated with forest-to-bog restoration, including due to processes far from restored sites. The LCA estimates mitigation timescales defined as the time following intervention at which the restored peatland is predicted to sequester or store more carbon than the forestry would have if retained. HighlightsO_LIHere we develop a novel forest-to-bog Life cycle assessment (LCA) tool C_LIO_LIThe LCA predicts carbon mitigation times following peatland restoration C_LIO_LIThe model combines a variety of process-based and empirical sub-models C_LIO_LIExample implementations for two different restoration scenarios are explored C_LIO_LISensitivity analysis highlights the model inputs that most impact outcomes C_LI Graphical abstract(A single, concise figure that serves as a visual summary of the main research findings described in your manuscript.) O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=80 SRC="FIGDIR/small/715261v1_ufig1.gif" ALT="Figure 1"> View larger version (18K): org.highwire.dtl.DTLVardef@f243f5org.highwire.dtl.DTLVardef@14bc4c7org.highwire.dtl.DTLVardef@164261borg.highwire.dtl.DTLVardef@1db3b_HPS_FORMAT_FIGEXP M_FIG The PEATREST Life cycle assessment (LCA) generates compound time series of carbon sequestration and carbon storage for two scenarios: the forest-to-bog peatland restoration (PR) and a counterfactual (CF) of forestry retention. By comparing the two scenarios, the LCA predicts the carbon mitigation timescales (vertical dashed lines). These are defined as the time following harvesting at which the peatland is predicted to sequester more (emit less), or to have stored more (lost less) carbon, than the forestry would have if retained. C_FIG

ecology↗

bioRxiv2023

GLYCOLYTIC REPROGRAMMING FUELS MYELOID CELL-DRIVEN HYPERCOAGULABILITY

BackgroundMyeloid cell metabolic reprogramming is a hallmark of inflammatory disease, however, its role in inflammation-induced hypercoagulability is poorly understood. Objective/MethodsUsing novel myeloid cell-based global haemostasis assays and murine models of immunometabolic disease, we evaluated the role of inflammation-associated metabolic reprogramming in regulating blood coagulation. ResultsGlycolysis was essential for enhanced activated myeloid cell tissue factor expression and decryption, driving increased cell-dependent thrombin generation in response to inflammatory challenge. Similarly, inhibition of glycolysis enhanced activated macrophage fibrinolytic activity via reduced plasminogen activator inhibitor 1 (PAI-1)-activity. Macrophage polarisation or activation markedly increased endothelial protein C receptor (EPCR) expression on monocytes and macrophages, leading to increased myeloid cell-dependent protein C activation. Importantly, inflammation-dependent EPCR expression on tissue-resident macrophages was also observed in vivo. Adipose tissue macrophages from obese mice fed a high-fat diet exhibited significantly enhanced EPCR expression and APC generation compared to macrophages isolated from the adipose tissue of healthy mice. Similarly, the induction of colitis in mice prompted infiltration of EPCR+ innate myeloid cells within inflamed colonic tissue that were absent from the intestinal tissue of healthy mice. ConclusionCollectively, this study identifies immunometabolic regulation of myeloid cell hypercoagulability, opening new therapeutic possibilities for targeted mitigation of thrombo-inflammatory disease. ESSENTIALSO_LIInflammation-mediated glycolytic reprogramming enables myeloid cell-induced hypercoagulability and antifibrinolytic activity. C_LIO_LI2-Deoxy-D-glucose (2-DG) inhibits the expression of transcription factors necessary for inflammation-induced procoagulant gene expression. C_LIO_LIMyeloid cell membrane regulation of tissue factor procoagulant activity is glycolysis-dependent. C_LIO_LIActivation of myeloid innate immunity dysregulates activated protein C anticoagulant pathway activity. C_LI

immunology↗

bioRxiv2021

Dexamethasone promotes breast cancer stem cells in obese and not lean mice

Obesity is highly prevalent in breast cancer patients and it is associated with increased recurrence and breast cancer specific mortality. Glucocorticoid (GC) use, in addition to obesity is associated with promoting breast cancer metastasis through activation of stemness-related pathways. Therefore, we utilised the synergetic allograft E0771 breast cancer model to investigate if treatment with GCs had differential effects on promoting cancer stem cells in lean and diet-induced obese mice. Indeed, both lean mice treated with dexamethasone and obese mice with no treatment had no effect on the ex vivo colony forming ability, mammosphere formation or ALDH bright subpopulation. However, treatment of obese mice with dexamethasone resulted in a significant increase in ex vivo colony formation, mammosphere formation, ALDH bright subpopulation and expression of pluripotency transcription factors. GC transcriptionally regulated genes were not altered in the dexamethasone treated groups compared to treatment controls. In summary, these results provide initial evidence that obesity presents a higher risk of GC induced cancer stemness via non-genomic GC signalling which is of potential translational significance.

cancer biology↗

bioRxiv2021

The immunophilin protein FKBPL and its peptide derivatives are novel regulators of vascular integrity and inflammation via NF-kappaB signaling

A breakdown in vascular integrity and excessive inflammation are hallmarks of serious pathological conditions including sepsis, acute respiratory distress syndrome (ARDs) and most recently, severe COVID-19. FK506 - binding protein like (FKBPL) is a member of the immunophilin protein superfamily with potent anti-tumor activity through inhibition of angiogenesis and cancer stemness. An FKBPL-based 23mer peptide, ALM201, displayed a good safety and pharmacokinetic profile in a Phase 1a oncology clinical trial and was subsequently designated orphan drug status by the FDA in ovarian cancer. Here we describe a novel role for FKBPL and its peptides in regulating vascular integrity and cytokine production though modulating NF-{kappa}B signaling. FKBPL knockdown promoted endothelial cell barrier permeability, which was further exacerbated upon stimulation with lipopolysaccharide (LPS) and accompanied by increased expression of TNF mRNA and phosphorylation of p65(RelA). Whilst treatment with the FKBPL based pre-clinical peptide, AD-01, increased VE-cadherin endothelial tight junctions following LPS stimulation. Bone marrow derived macrophages (BMDM) from FKBPL haploinsufficient mice (Fkbpl+/-) also demonstrated increased phosphorylation of p65(RelA) in response to LPS stimulation compared to wild-type mice. Furthermore, treatment with AD-01 inhibited p65(RelA) phosphorylation following LPS stimulation resulting in reduced NF-{kappa}B target gene expression and proinflammatory cytokine production. In an in vivo LPS survival model, Fkbpl+/- mice have reduced survival compared to wild-type mice. Moreover, treatment of wild-type mice with the clinical FKBPL-based peptide, ALM201, following LPS injection resulted in a 100% survival rate in mice at experimental endpoint, as well as an abrogation of production of pro-inflammatory cytokines, TNF and IL-6, in peritoneal lavage washings. Analysis of human genetic biobanks found an association between common genetic variants associated with FKBPL and traits associated with inflammatory disorders such as psoriasis, rheumatoid arthritis and high lymphocyte count. In summary, for the first time, we describe a novel role for FKBPL as a regulator of inflammation and vascular integrity through modulating NF-{kappa}B signaling and FKBPL based therapies demonstrate potent anti-inflammatory activity.

immunology↗