Structure-specific detection of plant cuticle bound residues of chlorothalonil by ELISA

Monoclonal antibodies (mAb) against the main photo-addition products of chlorothalonil with olefinic compounds of plant cuticles were produced. An indirect competitive enzyme-linked immunosorbent assay (ELISA) was developed for the detection of free and bound chlorothalonil and its derivatives. For the characterization of the binding properties of the mAb, derivatives of chlorothalonil (simulating structures of cuticle bound residues) were synthesized. The cross-reactivities of these products were determined by ELISA. The test system was employed to detect bound residues of chlorothalonil in enzymatically isolated tomato cuticles, which had been spiked with methanolic solutions of the compound, irradiated by simulated sunlight and extracted. The use of isolated cuticles allows work to be carried out with authentic material without disturbance by metabolic processes. © 1999 Society of Chemical Industry     

Nitrous oxide emissions from grass–clover swards as influenced by sward age and biological nitrogen fixation

Grassland renovation by cultivation and reseeding has been shown to increase short-term emissions of N₂O, but there is uncertainty about long-term effects, despite the potential impacts of reseeding on sward composition and soil functions. A field experiment was therefore carried out to determine how N₂O emissions from previously renovated grasslands varied in the intermediate to long-term, compared with an undisturbed permanent grassland (PG). Plots on the PG site were renovated, either two (G2) or five (G5) years prior to the two experimental years. In each sward age and experimental year, annual N₂O-measurements were conducted on a weekly basis and compared with the undisturbed PG. Plots were either unfertilized or were fertilized with slurry (240 kg N ha⁻¹ year⁻¹). On average, annual N₂O emissions were 0.39 kg N/ha for the unfertilized swards, and 0.91 kg N/ha for slurry-fertilized swards. Sward age had no effect on N₂O emissions. With increasing sward age the proportion of legumes in the sward was reduced, but a minimum biological nitrogen fixation (BNF) of 88 kg N/ha was maintained even in the fertilized PG. Both sward age and BNF were of limited importance for the annual N₂O emissions compared with the effects of soil carbon content and nitrogen surplus levels. However, measured N₂O emissions were low in all sward age treatments, with a low risk of additional N₂O emissions when BNF is taken into account in fertilizer planning.     

Efficacy and Mechanism of Action of Marine Alkaloid 3,10-Dibromofascaplysin in Drug-Resistant Prostate Cancer Cells

Efficacy and mechanism of action of marine alkaloid 3,10-dibromofascaplysin (DBF) were investigated in human prostate cancer (PCa) cells harboring different levels of drug resistance. Anticancer activity was observed across all cell lines examined without signs of cross-resistance to androgen receptor targeting agents (ARTA) or taxane based chemotherapy. Kinome analysis followed by functional investigation identified JNK1/2 to be one of the molecular targets of DBF in 22Rv1 cells. In contrast, no activation of p38 and ERK1/2 MAPKs was observed. Inhibition of the drug-induced JNK1/2 activation or of the basal p38 activity resulted in increased cytotoxicity of DBF, whereas an active ERK1/2 was identified to be important for anticancer activity of the alkaloid. Synergistic effects of DBF were observed in combination with PARP-inhibitor olaparib most likely due to the induction of ROS production by the marine alkaloid. In addition, DBF intensified effects of platinum-based drugs cisplatin and carboplatin, and taxane derivatives docetaxel and cabazitaxel. Finally, DBF inhibited AR-signaling and resensitized AR-V7-positive 22Rv1 prostate cancer cells to enzalutamide, presumably due to AR-V7 down-regulation. These findings propose DBF to be a promising novel drug candidate for the treatment of human PCa regardless of resistance to standard therapy.     

Study of Structure–Activity Relationships of the Marine Alkaloid Fascaplysin and Its Derivatives as Potent Anticancer Agents

Marine alkaloid fascaplysin and its derivatives are known to exhibit promising anticancer properties in vitro and in vivo. However, toxicity of these molecules to non-cancer cells was identified as a main limitation for their clinical use. Here, for the very first time, we synthesized a library of fascaplysin derivatives covering all possible substituent introduction sites, i.e., cycles A, C and E of the 12H-pyrido[1-2-a:3,4-b’]diindole system. Their selectivity towards human prostate cancer versus non-cancer cells, as well as the effects on cellular metabolism, membrane integrity, cell cycle progression, apoptosis induction and their ability to intercalate into DNA were investigated. A pronounced selectivity for cancer cells was observed for the family of di- and trisubstituted halogen derivatives (modification of cycles A and E), while a modification of cycle C resulted in a stronger activity in therapy-resistant PC-3 cells. Among others, 3,10-dibromofascaplysin exhibited the highest selectivity, presumably due to the cytostatic effects executed via the targeting of cellular metabolism. Moreover, an introduction of radical substituents at C-9, C-10 or C-10 plus C-3 resulted in a notable reduction in DNA intercalating activity and improved selectivity. Taken together, our research contributes to understanding the structure–activity relationships of fascaplysin alkaloids and defines further directions of the structural optimization.     

Liquid crystalline networks composed of pentagonal, square, and triangular cylinders

T-shaped molecules are designed in such a way that they self-organize into nanoscale liquid crystalline honeycombs based on polygons with any chosen number of sides. One of the phases reported here is a periodic organization of identical pentagonal cylinders; the other one is a structure composed of square-shaped and triangular cylinders in the ratio 2:1. These two different packing motifs represent duals of the same topological class. The generalization of the concept applied here allows the prediction of a whole range of unusual complex liquid crystalline phases.     

Species-specific recognition of single-stranded RNA via toll-like receptor 7 and 8

Double-stranded ribonucleic acid (dsRNA) serves as a danger signal associated with viral infection and leads to stimulation of innate immune cells. In contrast, the immunostimulatory potential of single-stranded RNA (ssRNA) is poorly understood and innate immune receptors for ssRNA are unknown. We report that guanosine (G)- and uridine (U)-rich ssRNA oligonucleotides derived from human immunodeficiency virus-1 (HIV-1) stimulate dendritic cells (DC) and macrophages to secrete interferon-alpha and proinflammatory, as well as regulatory, cytokines. By using Toll-like receptor (TLR)-deficient mice and genetic complementation, we show that murine TLR7 and human TLR8 mediate species-specific recognition of GU-rich ssRNA. These data suggest that ssRNA represents a physiological ligand for TLR7 and TLR8.     

Human neuroblasts migrate to the olfactory bulb via a lateral ventricular extension

The rostral migratory stream (RMS) is the main pathway by which newly born subventricular zone cells reach the olfactory bulb (OB) in rodents. However, the RMS in the adult human brain has been elusive. We demonstrate the presence of a human RMS, which is unexpectedly organized around a lateral ventricular extension reaching the OB, and illustrate the neuroblasts in it. The RMS ensheathing the lateral olfactory ventricular extension, as seen by magnetic resonance imaging, cell-specific markers, and electron microscopy, contains progenitor cells with migratory characteristics and cells that incorporate 5-bromo-2'-deoxyuridine and become mature neurons in the OB.     

Modelling seawater intrusion in the Burdekin Delta Irrigation Area,North Queensland,Australia

The Burdekin Delta is a major irrigation area situated in the dry tropics of North Queensland. It is unique in that (i) it overlies shallow groundwater systems that serve as a major water supply for the irrigation of sugarcane, and (ii) it is adjacent to the world heritage listed Great Barrier Reef. Water management practices include large recharge pits and surface spreading of water to assist with replenishment of the groundwater. This has been useful in maintaining groundwater levels to help control seawater intrusion. This technique, however, can be costly and ineffective in unconfined aquifer systems, which are subjected to large amounts of groundwater pumping for irrigation. There are more than 1800 production bores currently used for irrigation in the Burdekin Delta and the large volumes of water extracted have at times lowered the regional water tables and made it difficult to control seawater intrusion.