Synthetic and living micropropellers for convection-enhanced nanoparticle transport.

Nanoparticles (NPs) have emerged as an advantageous drug delivery platform for the treatment of various ailments including cancer and cardiovascular and inflammatory diseases. However, their efficacy in shuttling materials to diseased tissue is hampered by a number of physiological barriers. One hurdle is transport out of the blood vessels, compounded by difficulties in subsequent penetration into the target tissue. Here, we report the use of two distinct micropropellers powered by rotating magnetic fields to increase diffusion-limited NP transport by enhancing local fluid convection. In the first approach, we used a single synthetic magnetic microrobot called an artificial bacterial flagellum (ABF), and in the second approach, we used swarms of magnetotactic bacteria (MTB) to create a directable "living ferrofluid" by exploiting ferrohydrodynamics. Both approaches enhance NP transport in a microfluidic model of blood extravasation and tissue penetration that consists of microchannels bordered by a collagen matrix.

Female sticklebacks count alleles in a strategy of sexual selection explaining MHC polymorphism.

The origin and maintenance of polymorphism in major histocompatibility complex (MHC) genes in natural populations is still unresolved. Sexual selection, frequency-dependent selection by parasites and pathogens, and heterozygote advantage have been suggested to explain the maintenance of high allele diversity at MHC genes. Here we argue that there are two (non-exclusive) strategies for MHC-related sexual selection, representing solutions to two different problems: inbreeding avoidance and parasite resistance. In species prone to inadvertent inbreeding, partners should prefer dissimilar MHC genotypes to similar ones. But if the goal is to maximize the resistance of offspring towards potential infections, the choosing sex should prefer mates with a higher diversity of MHC alleles. This latter strategy should apply when there are several MHC loci, as is the case in most vertebrates. We tested the relative importance of an 'allele counting' strategy compared to a disassortative mating strategy using wild-caught three-spined sticklebacks (Gasterosteus aculeatus) from an interconnected system of lakes. Here we show that gravid female fish preferred the odour of males with a large number of MHC class-IIB alleles to that of males with fewer alleles. Females did not prefer male genotypes dissimilar to their own.

High-throughput nuclear magnetic resonance-based screening.

A high-throughput screening strategy is described that involves the acquisition of two-dimensional 15N/1H correlation spectra in less than 10 min on 50 microM protein samples using cryogenic NMR probe technology. By screening at these concentrations, small organic molecules can be tested in mixtures of 100, which dramatically increases the throughput of the NMR-based assay. Using this strategy, libraries of more than 200 000 compounds can be tested in less than 1 month. There are many advantages of high-throughput NMR-based screening compared to conventional assays, such as the ability to identify high-affinity ligands for protein targets with no known function. This suggests that the method will be extremely useful for screening the large number of targets derived from genomics research.

In vivo properties of N-(2-aminoethyl)-5-halogeno-2-pyridinecarboxamide 18F- and 123I-labelled reversible inhibitors of monoamine oxidase B.

The reversible and highly selective monoamine oxidase B (MAO-B) inhibitor Ro 19-6327, a picolinic acid derivative, was selected for the development of new radiopharmaceuticals, whereby in place of Cl either 123I or 18F was introduced. The respective labelling procedures have been described earlier. In this study, some metabolic properties were investigated. Blood and urine samples were analysed, and halogenated picolinylglycine, a more hydrophilic compound, was identified as the main metabolite. This shows that the amine is oxidised to the respective carboxylate, but the intermediate imine or aldehyde that was proposed earlier could not be detected. First experiments with single photon emission tomography and positron emission tomography (PET) showed that the iodo compound can be used to investigate MAO-B in vivo while the fluoro compound is accumulated in the brain to such a low degree that no PET studies can be performed. We conclude that the main reason for the poor uptake of the fluoro compound is its lower lipophilicity as compared to the iodo compound and, to a lesser degree, its metabolism, which is similar for both compounds.

[123I/18F] N-(2-aminoethyl)-5-halogeno-2-pyridinecarbox-amides, site specific tracers for MAO-B mapping with SPECT and PET.

After the successful 123I-labelling of Ro 43-0463 the new radiopharmaceutical was tested in animals and humans. Both investigations proved the binding of the labelled compound to cerebral MAO-B. SPECT investigations resulted in an imaging of the MAO-B distribution in the human brain. This prompted us to develop the labelling of this type of MAO-B inhibitor with 18F enabling us to transfer our results to PET.