Synthesis and in vitro evaluation of small-molecule [18F] labeled gonadotropin-releasing hormone (GnRH) receptor antagonists as potential PET imaging agents for GnRH receptor expression

Two novel small molecule gonadotropin-releasing hormone (GnRH) receptor antagonists (12 and 13) of the furamide-class were synthesized and evaluated in vitro for their receptor binding affinities for the rat GnRH receptor. Radiolabeling with no carrier added fluorine-18 of the appropriate precursors was investigated in a one-step reaction. Log P (Octanol/PBS pH 7.4) and serum stability of the compounds were investigated. The antagonists showed low nM affinity for the rat GnRH receptor. ¹⁸F-radiolabled compounds were obtained in high radiochemical purity (>95%) and specific activity (>75 GBq/μmol). These findings suggest this class of compounds holds promise as potential probes for PET targeting of GnRH-receptor expression.     

Aging-related changes in the sensitivity of the system of respiratory control and the intensity of free-radical processes in humans

Results of a comparative study of the sensitivity of the system of respiratory control to increases in the CO₂ concentration and the intensity of free-radical processes in young and elderly subjects are described. It is shown that normal (natural) aging is accompanied by a decrease in the sensitivity of the respiratory system to hypercapnic stimulation and a parallel significant decrease in the activity of catalase in the blood of examined subjects. Mechanisms responsible for the modifications of the sensitivity of the system of respiratory control to hypercapnia are discussed; these shifts can be at least partly related to changes in the intensity of production of free radicals observed in elderly subjects. Neirofiziologiya/Neurophysiology, Vol. 40, No. 1, pp. 53–57, January–February, 2008.     

On the variability of respiration in terrestrial ecosystems: moving beyond Q10

Respiration, which is the second most important carbon flux in ecosystems following gross primary productivity, is typically represented in biogeochemical models by simple temperature dependence equations. These equations were established in the 19th century and have been modified very little since then. Recent applications of these equations to data on soil respiration have produced highly variable apparent temperature sensitivities. This paper searches for reasons for this variability, ranging from biochemical reactions to ecosystem‐scale substrate supply. For a simple membrane‐bound enzymatic system that follows Michaelis–Menten kinetics, the temperature sensitivities of maximum enzyme activity (V_max) and the half‐saturation constant that reflects the affinity of the enzyme for the substrate (K_m) can cancel each other to produce no net temperature dependence of the enzyme. Alternatively, when diffusion of substrates covaries with temperature, then the combined temperature sensitivity can be higher than that of each individual process. We also present examples to show that soluble carbon substrate supply is likely to be important at scales ranging from transport across membranes, diffusion through soil water films, allocation to aboveground and belowground plant tissues, phenological patterns of carbon allocation and growth, and intersite differences in productivity. Robust models of soil respiration will require that the direct effects of substrate supply, temperature, and desiccation stress be separated from the indirect effects of temperature and soil water content on substrate diffusion and availability. We speculate that apparent Q₁₀ values of respiration that are significantly above about 2.5 probably indicate that some unidentified process of substrate supply is confounded with observed temperature variation.     

Identifying DOC gains and losses during a 20-year record in the Trout Beck catchment,Moor House,UK

The turnover of organic carbon in rivers could represent a large source of greenhouse gases to the atmosphere and studies have suggested that of the order of 70% of the dissolved organic carbon exported from soils could be lost in rivers before it flows to continental seas. The Environmental Change Network (ECN) monitoring of the dominantly peat-covered Trout Beck catchment within the Moor House site enabled the amount of dissolved organic carbon (DOC) lost within a stream over a 20-year period to be estimated. The study compared DOC concentrations of precipitation, shallow and deep soil waters with those at the catchment outlet. The mass balance between source and outlet was reconstructed by two methods: a single conservative tracer; and based upon a principal component analysis (PCA) using multiple tracers. The study showed the two methods had different outcomes, with the PCA showing a DOC gain and the single tracer showing a DOC loss. The DOC gain was attributed to an unmeasured groundwater contribution that dominates when the river discharge is lower. The DOC loss was related to the in-stream residence time, the soil temperature and month of the year, with longer in-stream residence times, warmer soils and summer months having larger DOC losses. The single tracer study suggested a 10 year average loss of 8.77 g C m⁻² year⁻¹, which is 33.1 g CO_2eq m⁻² year⁻¹, or 29% of the DOC flux from the source over a mean in-stream residence time of 4.33 h.