P-glycoprotein, the overexpression of which is a major cause for the failure of cancer chemotherapy in man, recognizes and transports a broad range of structurally unrelated amphiphilic compounds. This study reports on the localization of the binding site of P-glycoprotein for iodomycin, the Bolton-Hunter derivative of the anthracycline daunomycin. 125 I]iodomycin had been predominantly incorporated into the fragment 230 -312 of isoform I of hamster P-glycoprotein. According to models based on hydropathy plots, the amino acid sequence 230 -312 forms the distal part of transmembrane segment 4, the second cytoplasmic loop, and the proximal part of transmembrane segment 5 in the Nterminal half of P-glycoprotein. The binding site for iodomycin is recognized with high affinity by vinblastine and cyclosporin A. P-glycoprotein, which belongs to the large family of ABC 1 transporters (1), binds and transports a broad range of structurally unrelated compounds (2). Its overexpression may cause the phenomenon of multidrug resistance (MDR) during cancer chemotherapy, whereby the tumor cells become resistant to a variety of antineoplastic agents due to a reduced intracellular accumulation of drugs (2-4). The MDR phenotype can be overcome by modulators, i.e. substances that are bound by P-glycoprotein and inhibit its drug excluding function (3). The medically important substrates of P-glycoprotein comprise anticancer drugs such as Vinca alkaloids and anthracyclines (2-4) and approved drugs that turned out to be potent modulators such as verapamil (5, 6), calcium antagonists (7), and cyclosporins (8).The major issue of how P-glycoprotein can handle so many substrates has been mainly approached by photoaffinity labeling and mutagenesis studies. Mutants that arose spontaneously during drug selection of cells and thereby changed their resistance profile were detected in the first cytoplasmic loop of human MDR1 protein (Gly 185 3 Val) (9) and in transmembrane segment (TM) 6 of hamster P-glycoprotein (Gly 338 3 Ala/Ala 339 3 Pro) (10). Active mutagenesis identified further motifs and positions in the N-and C-terminal half of P-glycoprotein which influence substrate specificity (11, 12). For example, the exchange of amino acids in the first cytoplasmic loop (11), TM5, TM6, TM10, TM12 (13-16), and the cytosolic linker peptide (17) resulted in all in an altered multidrug resistance phenotype, suggesting that during binding and transport the substrate is recognized by multiple residues located either in the cytosolic, membraneous, or ectoplasmic domains.Hydropathy plots deduced from the primary sequence predict that P-glycoprotein consists principally of two symmetrical halves, each of which contain a membrane domain with six membrane-spanning segments and a subsequent cytosolic nucleotide binding fold (18 -20). The topology of P-glycoprotein in vivo, however, may be more variable than predicted, e.g. under certain experimental conditions, TM segments were detected outside the membrane and loops postulated to face the cytosol were foun...

Optical sensing technologies provide opportunities for in situ oxygen sensing capable of capturing the whole range of spatial and temporal variability. We developed a miniaturized Distributed Oxygen Sensor ("mDOS") specifically for long-term in situ application in soil and sediment. The mDOS sensor system enables the unattended, repeated acquisition of time series of in situ oxygen profiles at a subcentimeter resolution covering a depth of up to one meter. As compared to existing approaches, this provides the possibility to reveal highly variable and heterogeneous oxygen dynamics at a high, quasi-continuous resolution across both scales. The applicability of the mDOS to capture both intra- and interday fine-scale variability of spatiotemporal oxygen dynamics under varying hydrological conditions is exemplarily demonstrated. We specifically aim at estimating the dependency between oxygen dynamics and hydrologic conditions along the measured profiles. The mDOS system enables highly detailed insights into oxygen dynamics in various aquatic and terrestrial environments and in the inherent transition zones between them. It thus represents a valuable tool to capture oxygen dynamics to help disentangling the coupling between underlying hydrological and biogeochemical process dynamics.

The effects of experimental inundation on invertebrate communities in artificial flumes fed with treated wastewater were investigated. Flumes, designed to simulate intermittent river conditions, were planted with 3 species of helophytes widely used in river restoration around the water‐stressed regions of Europe. Different species of vegetation had different capabilities to reduce the invertebrate's negative reaction to inundation, related mostly to rhizosphere density. Of the 3 helophyte species tested, only 1, Lysimachia vulgaris, showed significant capabilities to reduce invertebrate negative reaction on inundation. Species richness of invertebrates before and after the inundation did not change in any of the flumes, whereas species density significantly declined in all flumes except one planted with L. vulgaris. This helophyte species was associated with high densities of the Culicidae larvae (common mosquitos), which has severe implications for river restoration and vector management in the region. This study indicates that the selection and establishment of different helophyte species will impact invertebrate communities in restored streams, especially streams experiencing variable inundation conditions.