Impact of microbial activity on the leaching of soluble N forms in soil

The hydrological transport of low-molecular weight organic nitrogen (LMWON) compounds has received little attention in the literature, particularly relative to inorganic nitrogen (N), with less attention given to the decoupling of the carbon (C) and N cycles following rainfall events. We determined the impacts of the soil biota on the transport of N compounds in a loam soil, using 15N and 13C to trace the vertical transport of 15N13C-urea, 15N13C-amino acids, 15NO3, and 15NH4 through the soil profile, following simulated rainfall events. This research has demonstrated that biotic assimilation leads to rapid decoupling of the C and N cycles during leaching, with C transport limited to the soil surface (< 2 cm), whereas N which was stored within the soil profile during a single rainfall event could be remobilised and leached (a further 2–6 cm) following an additional rainfall event

Nutrient stripping: the global disparity between food security and soil nutrient stocks

1. The Green Revolution successfully increased food production but in doing so created a legacy of inherently leaky and unsustainable agricultural systems. Central to this are the problems of excessive nutrient mining. If agriculture is to balance the needs of food security with the delivery of other ecosystem services, then current rates of soil nutrient stripping must be reduced and the use of synthetic fertilisers made more efficient. 2. We explore the global extent of the problem, with specific emphasis on the failure of macronutrient management (e.g. nitrogen, phosphorus) to deliver continued improvements in yield and the failure of agriculture to recognise the seriousness of micronutrient depletion (e.g. copper, zinc, selenium). 3. Nutrient removals associated with the relatively immature, nutrient-rich soils of the UK are contrasted with the mature, nutrient-poor soils of India gaining insight into the emerging issue of nutrient stripping and the long-term implications for human health and soil quality. Whilst nutrient deficiencies are rare in developed countries, micronutrient deficiencies are commonly increasing in less-developed countries. Increasing rates of micronutrient depletion are being inadvertently accomplished through increasing crop yield potential and nitrogen fertiliser applications. 4. Amongst other factors, the spatial disconnects caused by the segregation and industrialisation of livestock systems, between rural areas (where food is produced) and urban areas (where food is consumed and human waste treated) are identified as a major constraint to sustainable nutrient recycling. 5. Synthesis and applications. This study advocates that agricultural sustainability can only be accomplished using a whole-systems approach that thoroughly considers nutrient stocks, removals, exports and recycling. Society needs to socially and environmentally re-engineer agricultural systems at all scales. It is suggested that this will be best realised by national-scale initiatives. Failure to do so will lead to an inevitable and rapid decline in the delivery of provisioning services within agricultural systems

From Molecular Cores to Planet-forming Disks: An SIRTF Legacy Program

Crucial steps in the formation of stars and planets can be studied only at mid‐ to far‐infrared wavelengths, where the Space Infrared Telescope (SIRTF) provides an unprecedented improvement in sensitivity. We will use all three SIRTF instruments (Infrared Array Camera [IRAC], Multiband Imaging Photometer for SIRTF [MIPS], and Infrared Spectrograph [IRS]) to observe sources that span the evolutionary sequence from molecular cores to protoplanetary disks, encompassing a wide range of cloud masses, stellar masses, and star‐forming environments. In addition to targeting about 150 known compact cores, we will survey with IRAC and MIPS (3.6–70 μm) the entire areas of five of the nearest large molecular clouds for new candidate protostars and substellar objects as faint as 0.001 solar luminosities. We will also observe with IRAC and MIPS about 190 systems likely to be in the early stages of planetary system formation (ages up to about 10 Myr), probing the evolution of the circumstellar dust, the raw material for planetary cores. Candidate planet‐forming disks as small as 0.1 lunar masses will be detectable. Spectroscopy with IRS of new objects found in the surveys and of a select group of known objects will add vital information on the changing chemical and physical conditions in the disks and envelopes. The resulting data products will include catalogs of thousands of previously unknown sources, multiwavelength maps of about 20 deg^2 of molecular clouds, photometry of about 190 known young stars, spectra of at least 170 sources, ancillary data from ground‐based telescopes, and new tools for analysis and modeling. These products will constitute the foundations for many follow‐up studies with ground‐based telescopes, as well as with SIRTF itself and other space missions such as SIM, JWST, Herschel, and TPF/Darwin

Diphosphine Bioconjugates via Pt(0)-Catalyzed Hydrophosphination. A Versatile Chelator Platform for Technetium-99m and Rhenium-188 Radiolabeling of Biomolecules

The ability to append targeting biomolecules to chelators that efficiently coordinate to the diagnostic imaging radionuclide, 99mTc, and the therapeutic radionuclide, 188Re, can potentially enable receptor-targeted “theranostic” treatment of disease. Here we show that Pt(0)-catalyzed hydrophosphination reactions are well-suited to the derivatization of diphosphines with biomolecular moieties enabling the efficient synthesis of ligands of the type Ph2PCH2CH2P(CH2CH2-Glc)2 (L, where Glc = a glucose moiety) using the readily accessible Ph2PCH2CH2PH2 and acryl derivatives. It is shown that hydrophosphination of an acrylate derivative of a deprotected glucose can be carried out in aqueous media. Furthermore, the resulting glucose-chelator conjugates can be radiolabeled with either 99mTc(V) or 188Re(V) in high radiochemical yields (&gt;95%), to furnish separable mixtures of cis- and trans-[M(O)2L2]+ (M = Tc, Re). Single photon emission computed tomography (SPECT) imaging and ex vivo biodistribution in healthy mice show that each isomer possesses favorable pharmacokinetic properties, with rapid clearance from blood circulation via a renal pathway. Both cis-[99mTc(O)2L2]+ and trans-[99mTc(O)2L2]+ exhibit high stability in serum. This new class of functionalized diphosphine chelators has the potential to provide access to receptor-targeted dual diagnostic/therapeutic pairs of radiopharmaceutical agents, for molecular 99mTc SPECT imaging and 188Re systemic radiotherapy.</p

Examination of the cytotoxic and embryotoxic potential and underlying mechanisms of next-generation synthetic trioxolane and tetraoxane antimalarials

Semisynthetic artemisinin-based therapies are the first-line treatment for P. falciparum malaria, but next-generation synthetic drug candidates are urgently required to improve availability and respond to the emergence of artemisinin-resistant parasites. Artemisinins are embryotoxic in animal models and induce apoptosis in sensitive mammalian cells. Understanding the cytotoxic propensities of antimalarial drug candidates is crucial to their successful development and utilization. Here, we demonstrate that, similarly to the model artemisinin artesunate (ARS), a synthetic tetraoxane drug candidate (RKA182) and a trioxolane equivalent (FBEG100) induce embryotoxicity and depletion of primitive erythroblasts in a rodent model. We also show that RKA182, FBEG100 and ARS are cytotoxic toward a panel of established and primary human cell lines, with caspase-dependent apoptosis and caspase-independent necrosis underlying the induction of cell death. Although the toxic effects of RKA182 and FBEG100 proceed more rapidly and are relatively less cell-selective than that of ARS, all three compounds are shown to be dependent upon heme, iron and oxidative stress for their ability to induce cell death. However, in contrast to previously studied artemisinins, the toxicity of RKA182 and FBEG100 is shown to be independent of general chemical decomposition. Although tetraoxanes and trioxolanes have shown promise as next-generation antimalarials, the data described here indicate that adverse effects associated with artemisinins, including embryotoxicity, cannot be ruled out with these novel compounds, and a full understanding of their toxicological actions will be central to the continuing design and development of safe and effective drug candidates which could prove important in the fight against malaria