Neurotoxicity of Alzheimer's disease A�� peptides is induced by small changes in the A��42 to A��40 ratio

The amyloid peptides Aβ₄₀ and Aβ₄₂ of Alzheimer's disease are thought to contribute differentially to the disease process. Although Aβ₄₂ seems more pathogenic than Aβ₄₀, the reason for this is not well understood. We show here that small alterations in the Aβ₄₂:Aβ₄₀ ratio dramatically affect the biophysical and biological properties of the Aβ mixtures reflected in their aggregation kinetics, the morphology of the resulting amyloid fibrils and synaptic function tested in vitro and in vivo. A minor increase in the Aβ₄₂:Aβ₄₀ ratio stabilizes toxic oligomeric species with intermediate conformations. The initial toxic impact of these Aβ species is synaptic in nature, but this can spread into the cells leading to neuronal cell death. The fact that the relative ratio of Aβ peptides is more crucial than the absolute amounts of peptides for the induction of neurotoxic conformations has important implications for anti‐amyloid therapy. Our work also suggests the dynamic nature of the equilibrium between toxic and non‐toxic intermediates.     

Habitat structure modified by an invasive grass enhances inundation withstanding in a salt-marsh wolf spider

Vegetation and underground structures are known to influence flood avoidance and flood resistance in invertebrates. In bimonthly-flooded European salt marshes, recent invasions by the nitrophilous grass Elymus athericus strongly modified usual habitat structure, notably by the production of a deep litter layer. Consequently, invaded habitats provide more interstitial spaces that may act as a refuge during flood events. By using both controlled and field designs, we tested whether invaded habitats may change the ability to resist flooding by the creation of new refuges during tides for a ground-living, predatory arthropod. The wolf spider Arctosa fulvolineata was employed as a model species since it occurs abundantly in both invaded and uninvaded salt-marsh habitats. In the field, its abundance strongly decreased (divided by three) after tidal flooding in uninvaded habitats by but did not change in invaded patches. Under controlled laboratory conditions, ten times more individuals withstood simulated flooding in the presence of litter and less decided to float. The presence of litter did not influence flood resistance, i.e. survival underwater. Our results show that habitat structure (i.e. the presence of litter) influences flood-avoiding behavior of A. fulvolineata, by providing more refuges. As the invasion of E. athericus alters salt-marsh habitat structure, it may enhance population size of a rare predatory spider by changing its behavior during flooding and resulting in less deleterious impacts of tides. Yet biological invasions are detrimental for biodiversity conservation, our study shows that an invasive species might indirectly benefit a few mobile rare species in a flood-disturbed habitat.     

Habitat Use and Mobility of Two Threatened Coastal Dune Insects: Implications for Conservation

We studied the habitat use and mobility of the Grayling butterfly (Hipparchia semele) and the Blue-Winged Grasshopper (Oedipoda caerulescens), two threatened insects within spatially structured blond and grey dunes in a nature reserve along the Belgian coast. Although both species occur in the same biotope, H. semele were more abundant in open, dynamic sites with a relatively high amount of bare sand, while O. caerulescens preferred sheltered, more stable environments with a lower amount of bare sand. Unlike H. semele, substrate use varied in accordance to body colouration in O. caerulescens, especially on cold days, with light-coloured animals being more abundant on sand and dark-coloured animals more abundant on moss. During a mark-recapture-study, we marked 493 Grayling butterflies and 1289 Blue-Winged Grasshoppers. On average, both sexes of H. semele were equally mobile (about 150 m/day; maximum recorded distance of about 1700 m) while male O. caerulescens were significantly more mobile than females (daily average 47 vs. 5 m; maximum distances observed for O. caerulescens were about 800 m). The importance of habitat heterogeneity (within and among patches) and the consequences of habitat use and mobility of both species for the conservation of typical coastal dune habitats are discussed. The complementary use of species-specific information to site-based management measures is advocated.     

Preparation and stability of lipid-coated nanocapsules of cisplatin: anionic phospholipid specificity

Cisplatin nanocapsules represent a novel lipid formulation of the anti-cancer drug cis-diamminedichloroplatinum(II) (cisplatin), in which nanoprecipitates of cisplatin are coated by a phospholipid bilayer consisting of a 1:1 mixture of zwitterionic phosphatidylcholine (PC) and negatively charged phosphatidylserine (PS). Cisplatin nanocapsules are characterized by an unprecedented cisplatin-to-lipid ratio and exhibit increased in vitro cytotoxicity compared to the free drug [Nat. Med. 8, (2002) 81]. In the present study, the stability of the cisplatin nanocapsules was optimized by varying the lipid composition of the bilayer coat and monitoring in vitro cytotoxicity and the release of contents during incubations in water and in mouse serum. The release of cisplatin from the PC/PS (1:1) nanocapsules in water increased with increasing temperature with a t(1/2) of 6.5 h at 37 degrees C. At 4 degrees C, cisplatin was retained in the nanocapsules for well over 8 days. Replacement of PS by either phosphatidylglycerol or phosphatidic acid revealed that nanocapsules prepared of PS were more stable, which was found to be due to the ability of PS to form a stable cisplatin-PS coordination complex. Mouse serum had a strong destabilizing effect on the cisplatin nanocapsules. The PC/PS formulation lost over 80% of cisplatin within minutes after resuspension in serum. Incorporation of poly(ethylene glycol 2000) (PEG)-derivatized phosphatidylethanolamine and cholesterol in the bilayer coat extended the lifetime of the cisplatin nanocapsules in mouse serum to almost an hour. The results demonstrate that specificity in the interaction of cisplatin with anionic phospholipids is an important criterium for the formation and stability of cisplatin nanocapsules.     

Efficient in vitro and in vivo excision of floxed sequences with a high-capacity adenoviral vector expressing Cre recombinase

Conditional gene expression or gene disruption using Cre/loxP- or FLP/frt-based recombination systems are valuable tools for studying gene function in development and disease. Recombinant adenoviral vectors expressing Cre recombinase have been suggested as an alternative for deletion of floxed sequences. To further improve this approach we generated a high-capacity adenoviral (HC-Ad) vector expressing Cre (HC-Adcre). In this vector all viral coding sequences are deleted resulting in decreased toxicity. In the present study HC-Adcre efficiently mediated recombination between two loxP sites located in the genome of a reporter cell line. When intravenously injected into ROSA26 reporter mice, a floxed sequence was excised in hepatocytes resulting in expression of the beta-gal reporter. Our data indicate that HC-Ad vectors expressing Cre effectively delete floxed sequences in vivo and have a significant potential as a tool for functional studies in mice.     

Starvation affects pre-dispersal behaviour of Erigone spiders

Population studies often focus on demographic and genetic consequences of dispersal strategies, generally within an evolutionary framework. Adaptive investment in dispersal is generally assessed from single types of (pre-)dispersal behaviour that are presumed to reliably reflect the dispersal strategy adopted. Various spider families show a striking and quantifiable display, known as tiptoe behaviour that prepares individuals for take-off prior to (passive) aerial dispersal (ballooning). The lack of efficient control mechanisms during ballooning prevents individuals from actively selecting a suitable habitat for landing. Ballooning dispersal is therefore often regarded as a wind lottery preceded by individual-based risk assessment. Our laboratory experiments showed that the duration of tiptoe behaviour can be used as an indicator of silk thread length, which is related to the potential dispersal distance. For two related species, Erigone arctica and E. dentiplapis, tiptoe duration decreased independently of sex after starvation, while more complex reaction norms were observed for tiptoe frequency.

Because these two aspects of dispersal behaviours show different responses towards a simple stress-factor (starvation) in two related spider species, we conclude that the level of plasticity in dispersal investment can be subject to selective forces affecting different dispersal properties in different ways. Our results, hence, plead for a more holistic approach when addressing evolutionary and applied questions related to dispersal.     

Ex Situ Normothermic Machine Perfusion of Donor Livers

In contrast to conventional static cold preservation (0-4 °C), ex situ machine perfusion may provide better preservation of donor livers. Continuous perfusion of organs provides the opportunity to improve organ quality and allows ex situ viability assessment of donor livers prior to transplantation. This video article provides a step by step protocol for ex situ normothermic machine perfusion (37 °C) of human donor livers using a device that provides a pressure and temperature controlled pulsatile perfusion of the hepatic artery and continuous perfusion of the portal vein. The perfusion fluid is oxygenated by two hollow fiber membrane oxygenators and the temperature can be regulated between 10 °C and 37 °C. During perfusion, the metabolic activity of the liver as well as the degree of injury can be assessed by biochemical analysis of samples taken from the perfusion fluid. Machine perfusion is a very promising tool to increase the number of livers that are suitable for transplantation.     

What Cues Do Ungulates Use to Assess Predation Risk in Dense Temperate Forests?

Anti-predator responses by ungulates can be based on habitat features or on the near-imminent threat of predators. In dense forest, cues that ungulates use to assess predation risk likely differ from half-open landscapes, as scent relative to sight is predicted to be more important. We studied, in the Białowieża Primeval Forest (Poland), whether perceived predation risk in red deer (Cervus elaphus) and wild boar (Sus scrofa) is related to habitat visibility or olfactory cues of a predator. We used camera traps in two different set-ups to record undisturbed ungulate behavior and fresh wolf (Canis lupus) scats as olfactory cue. Habitat visibility at fixed locations in deciduous old growth forest affected neither vigilance levels nor visitation rate and cumulative visitation time of both ungulate species. However, red deer showed a more than two-fold increase of vigilance level from 22% of the time present on control plots to 46% on experimental plots containing one wolf scat. Higher vigilance came at the expense of time spent foraging, which decreased from 32% to 12% while exposed to the wolf scat. These behavioral changes were most pronounced during the first week of the experiment but continuous monitoring of the plots suggested that they might last for several weeks. Wild boar did not show behavioral responses indicating higher perceived predation risk. Visitation rate and cumulative visitation time were not affected by the presence of a wolf scat in both ungulate species. The current study showed that perceived predation risk in red deer and wild boar is not related to habitat visibility in a dense forest ecosystem. However, olfactory cues of wolves affected foraging behavior of their preferred prey species red deer. We showed that odor of wolves in an ecologically equivalent dose is sufficient to create fine-scale risk factors for red deer.     

Fitness and predation potential of Macrolophus pygmaeus reared under artificial conditions

Abstract The biological parameters of Macrolophus pygmaeus Rambur after prolonged rearing in the absence of plant materials were compared with those of conventionally plant‐reared predators. When eggs of Ephestia kuehniella Zeller were provided as food, developmental and reproductive fitness of M. pygmaeus reared for over 30 consecutive generations using artificial living and oviposition substrates was similar to that of predators kept on tobacco leaves. Plantless‐reared fifth instars of the predator also had similar predation rates on second instars of the tobacco aphid, Myzus persicae nicotianae Blackman, as their peers maintained on plant materials. In a further experiment, predation on aphid prey by fifth instar M. pygmaeus fed one of two egg yolk‐based artificial diets was compared with that of nymphs fed E. kuehniella eggs. Despite their lower body weights, predators produced on either artificial diet killed similar numbers of prey as their counterparts reared on lepidopteran eggs. Our study indicates that artificial rearing systems may be useful to further rationalize the production of this economically important biological control agent.