Glucose-lactate metabolic cooperation in cancer: insights from a spatial mathematical model and implications for targeted therapy

A recent study has hypothesised a glucose–lactate metabolic symbiosis between adjacent hypoxic and oxygenated regions of a developing tumour, and proposed a treatment strategy to target this symbiosis. However, in vivo experimental support remains inconclusive. Here we develop a minimal spatial mathematical model of glucose–lactate metabolism to examine, in principle, whether metabolic symbiosis is plausible in human tumours, and to assess the potential impact of inhibiting it. We find that symbiosis is a robust feature of our model system—although on the length scale at which oxygen supply is diffusion-limited, its occurrence requires very high cellular metabolic activity—and that necrosis in the tumour core is reduced in the presence of symbiosis. Upon simulating therapeutic inhibition of lactate uptake, we predict that targeted treatment increases the extent of tissue oxygenation without increasing core necrosis. The oxygenation effect is correlated strongly with the extent of wild-type hypoxia and only weakly with wild-type symbiotic behaviour, and therefore may be promising for radiosensitisation of hypoxic, lactate-consuming tumours even if they do not exhibit a spatially well-defined symbiosis. Finally, we conduct in vitro experiments on the U87 glioblastoma cell line to facilitate preliminary speculation as to where highly malignant tumours might fall in our parameter space, and find that these experiments suggest a weakly symbiotic regime for U87 cells, thus raising the new question of what relationship might exist between symbiosis and tumour malignancy

Abrupt reversal in emissions and atmospheric abundance of HCFC-133a (CF3CH2Cl)

Hydrochlorofluorocarbon HCFC-133a (CF3CH2Cl) is an anthropogenic compound whose consumption for emissive use is restricted under the Montreal Protocol. A recent study showed rapidly increasing atmospheric abundances and emissions. We report that, following this rise, the at- mospheric abundance and emissions have declined sharply in the past three years. We find a Northern Hemisphere HCFC-133a increase from 0.13 ppt (dry air mole fraction in parts-per-trillion) in 2000 to 0.50 ppt in 2012–mid-2013 followed by an abrupt reversal to 0.44 ppt by early 2015. Global emissions derived from these observations peaked at 3.1 kt in 2011, followed by a rapid decline of 0.5 kt yr−2 to 1.5 kt yr−1 in 2014. Sporadic HCFC-133a pollution events are detected in Europe from our high-resolution HCFC-133a records at three European stations, and in Asia from sam- ples collected in Taiwan. European emissions are estimated to be <0.1 kt yr−1 although emission hotspots were identi- fied in France

Modelling collective cell behaviour

The classical mean-field approach to modelling biological systems makes a number of simplifying assumptions which typically lead to coupled systems of reaction-diffusion partial differential equations. While these models have been very useful in allowing us to gain important insights into the behaviour of many biological systems, recent experimental advances in our ability to track and quantify cell behaviour now allow us to build more realistic models which relax some of the assumptions previously made. This brief review aims to illustrate the type of models obtained using this approach

UV and infrared absorption spectra, atmospheric lifetimes, and ozone depletion and global warming potentials for CCl₂FCCl₂F (CFC-112), CCl₃CClF₂ (CFC-112a), CCl₃CF₃ (CFC-113a), and CCl₂FCF₃ (CFC-114a)

The potential impact of CCl2FCF3 (CFC-114a) and the recently observed CCl2FCCl2F (CFC-112), CCl3CClF2 (CFC-112a), and CCl3CF3 (CFC-113a) chlorofluorocarbons (CFCs) on stratospheric ozone and climate is presently not well characterized. In this study, the UV absorption spectra of these CFCs were measured between 192.5 and 235 nm over the temperature range 207–323 K. Precise parameterizations of the UV absorption spectra are presented. A 2-D atmospheric model was used to evaluate the CFC atmospheric loss processes, lifetimes, ozone depletion potentials (ODPs), and the associated uncertainty ranges in these metrics due to the kinetic and photochemical uncertainty. The CFCs are primarily removed in the stratosphere by short-wavelength UV photolysis with calculated global annually averaged steady-state lifetimes (years) of 63.6 (61.9–64.7), 51.5 (50.0–52.6), 55.4 (54.3–56.3), and 105.3 (102.9–107.4) for CFC-112, CFC-112a, CFC-113a, and CFC-114a, respectively. The range of lifetimes given in parentheses is due to the 2σ uncertainty in the UV absorption spectra and O(1D) rate coefficients included in the model calculations. The 2-D model was also used to calculate the CFC ozone depletion potentials (ODPs) with values of 0.98, 0.86, 0.73, and 0.72 obtained for CFC-112, CFC-112a, CFC-113a, and CFC-114a, respectively. Using the infrared absorption spectra and lifetimes determined in this work, the CFC global warming potentials (GWPs) were estimated to be 4260 (CFC-112), 3330 (CFC-112a), 3650 (CFC-113a), and 6510 (CFC-114a) for the 100-year time horizon

Notes on British spiders, with descriptions of new species

Volume: 15Start Page: 25End Page: 4

Projected impact, costs and savings from the VMMC program in a 'status quo' background context, relative to the counterfactual scenario of no VMMC program ever.

<p>Projected impact, costs and savings from the VMMC program in a 'status quo' background context, relative to the counterfactual scenario of no VMMC program ever.</p