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Speakman, C.

Publications and source records attributed to Speakman, C..

3 recordsLinked to original sources

Using stochastic dynamic programming for making decisions about invasive species

1. Invasive species pose significant ecological, economic, and public health challenges. Their management requires repeated decisions under uncertainty about when, where and how intensively to intervene. Although structured decision-making and adaptive management provide conceptual frameworks for addressing these challenges, their practical implementation remains limited because optimization methods such as stochastic dynamic programming (SDP) are often perceived as mathematically complex, challenting to apply and difficult to interpret. 2. Here, we provide a practical guide to using SDP and its extensions for invasive species management. Using coypu (*Myocastor coypus*) management as a running case study, we introduce the framework through a minimal working example before progressively extending it to spatial dynamics, imperfect detection using partially observable Markov decision processes (POMDPs), adaptive management under model uncertainty, and value-of-information analyses that quantify the benefits of learning before acting. 3. All examples are accompanied by reproducible implementations in R, together with recommendations on model formulation, parameterization and interpretation. We also discuss the strengths and limitations of SDP. 4. By lowering the technical barrier to SDP, this guide aims to help ecologists and wildlife managers integrate decision theory into invasive species management, enabling transparent, reproducible and objective-driven management strategies under uncertainty. More broadly, the methods presented here are applicable to a wide range of ecological decision problems beyond invasive species, wherever management requires balancing immediate actions against uncertain future outcomes.

ecology↗

Pyruvate from bone marrow mesenchymal stem cells supports myeloma redox homeostasis and anabolism

Multiple myeloma is an incurable cancer of plasma cells that depends on the bone marrow for its survival. Despite its prevalence, the molecular mechanisms underlying this malignancy remain poorly understood. In this study, we aim to bridge this knowledge gap by elucidating the metabolic interplay between myeloma cells and bone marrow mesenchymal stem cells (BMMSCs). BMMSCs are crucial in supporting myeloma cell metabolism, contributing to their proliferation, survival, and resistance to chemotherapy. Through a combination of mathematical modelling and experimental co-cultures, we demonstrate that pyruvate - the end product of glycolysis - plays a key role in myeloma cell metabolism. Our findings reveal that myeloma cells predominantly rely on the uptake of pyruvate produced by neighbouring BMM-SCs via the plasma membrane proton-linked monocarboxylate transporters MCT-1 and MCT-2 encoded by the Slc16a1 and a2 genes, respectively. Furthermore, we show that pharmacological inhibition of the MCT-1/2, with AZD3965, triggers a cascade of compensatory metabolic responses, disrupting redox balance and significantly reducing the proliferation capacity of co-cultured myeloma cells.

cancer biology↗

Guardian crypt-base-goblet-cells protect the human colonic stem cell niche by triggering cholinergic calcium signal-dependent MUC2 secretion and luminal flushing

Mucus secreting goblet cells play a vital role in the maintenance of tissue homeostasis. Here we report the discovery of an enigmatic mechanism for the generation of calcium signals that couple cholinergic input to secretion of hydrated mucus in the human colonic stem cell niche. Mechanistic insights for this study were derived from native human colonic crypts and crypt-like organoids expressing MUC2-mNEON. Importantly, we demonstrate that the human colonic stem cell niche is also a cholinergic niche, and that activation of muscarinic receptors initiates calcium signals at the apical pole of intestinal stem cells and neighbouring crypt-base-goblet-cells. The calcium signal trigger zone is defined by a microdomain of juxtaposed calcium stores expressing TPC1 and InsP3R3 calcium channels. Co-activation of TPC1 and InsP3R3 is required for generation of cholinergic calcium signals and downstream secretion of hydrated mucus, which culminates in the flushing of the colonic stem cell niche.

cell biology↗