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.     

How much of the vertebrate diversity of sub-Saharan Africa is catered for by recent conservation proposals?

A database documenting the distribution of birds, mammals, amphibians and snakes across 1° latitude and longitude squares of mainland sub-Saharan Africa provides an opportunity to quantify how many of these vertebrates are potentially catered for by recent large-scale conservation proposals. Sets of priority areas proposed by BirdLife International, the World Wildlife Fund (USA), the World Conservation Union and the World Wide Fund for Nature, Conservation International, and the World Resources Institute contain between 45 and 93% of 3752 species of birds, mammals, snakes and amphibians breeding in this area. Gaps in the coverage of vertebrates were found in all large-scale proposals, and these are mapped. Most of the conservation proposals perform better than random selection of similar sized areas of Africa, with the proposals focused on species performing more efficiently than schemes based on large areas of intact habitat or process-related criteria. Four of the schemes approach the performance of a complementarity-based algorithm that aims to maximise the number of species captured within a given area of land, and which has been widely advocated as a tool for conservation planning. The reasons for this are discussed and the relevance of the results for conservation planning at coarse and fine scales are explained.     

Influence of exercise on horses' limb volume, measured by an optoelectronic device

This study tested for the first time an optoelectronic device (Perometer*) measuring limb volume of horses. An analysis of its application was performed regarding the influence of different types of physical exercise on the volume of the extremities. 40 horses were divided into four groups often horses, each group being exposed to exercise, differing in kind and duration of lunging, horse-ridden and riderless. The volume measurement was performed by determining the inactive value (I) after a twelfe-hour standing period, the load value (II) immediately after exercise and recovery value (III) one hour after exercise. The results showed a highly significant decrease in limb volume of 5.7% between values (I) and (II), as well as a highly significant increase of 68% between (II) and (III). The volume changes observed in male horses were significantly higher than in female horses. Volume changes in horse-ridden groups were higher than riderless ones, but not significant. There were fewer leg volume changes at low ambient temperatures (1-12 degrees C) compared to high temperatures (23-31 degrees C), but these were not statistically significant. Well-trained horses showed lower volume changes than less trained horses (not statistically significant). The Perometer is a fast and reliable tool for measuring limb volume of horses. The ICC (Interclass Correlation Coefficient) calculated a high measurement reproducibility of 0.996. A variance analysis showed no significant differences between the three repeated leg measurements. Thus, the Perometer can be used for monitoring and quantifying edema and documenting limb volume changes resulting from training, wearing compression stockings or bandages, manual lymph drainage.     

Landscape elements as potential barriers and corridors for bees, wasps and parasitoids

Habitat loss and fragmentation in agricultural landscapes lead to severe declines of abundance and richness of many insect species in the remaining isolated semi-natural habitats. We analysed possible barrier effects of large hedges and corridor effects of narrow grass strips that were hypothesized to affect foraging and dispersal of hymenopterans. We selected calcareous grasslands in the vicinity of Göttingen (Germany), which harbour high Hymenoptera diversity and are starting points for foraging and dispersal in the landscape. We installed pan traps to sample bees (i) on the grasslands; (ii) on grassland edges behind adjacent hedges (potential barriers) and without hedges; (iii) on grass strips in 100 m distance to the grassland, which were connected or unconnected to the grassland; and (iv) unconnected (isolated) grass strips in 300 m and 750 m distance to test for corridor and isolation effects on abundance and species richness of foraging wild bees. Additionally we provided trap nests for bees, wasps and their parasitoids on the grasslands and the strips. Species abundance and richness declined with increasing isolation from grasslands for foraging solitary bees, trap-nesting bees, wasps and parasitoids, but not for foraging bumblebees. Hedges did not confine movement of foraging bees. We found no mitigating effects of (100 m) corridor strips on any of the observed groups. We conclude that conservation of semi-natural habitats as sources of bee and wasp diversity is important and that grass strips act as sinks rather than corridors when high quality patches are nearby.