Influence of net charge on the aggregation and solubility behaviour of amphotericin B and its derivatives in aqueous media

The poor solubility of polyene antibiotics in aqueous media limits their application in the therapy of systemic fungal infections. In the present paper we have demonstrated that the ionic state (net electrical charge) of the antibiotic molecule is an important factor in determining the aggregation and solubility properties of amphotericin B and its derivatives. A multi-step model of polyene self-association in aqueous media has been proposed as an explanation for the fact that some major differences are observed when aggregation is monitored by different techniques. Offprint requests to: J. Mazerski     

Defensive secretions of larvae of a carabid beetle

Secretions of an eversible gland on the metathorax of larvae of Chlaenius cordicollis Kirby (Coleoptera: Carabidae) are investigated by headspace analysis using solid phase microextraction followed by gas chromatography‐mass spectrometry (GC‐MS). Larvae from Manitoba, Canada and Pennsylvania, U.S.A., are sampled. Nine presumed defensive compounds are detected when the gland is everted, and this represents the first characterization of defensive secretions of larvae of a carabid beetle. With the exception of a single component (2‐methoxy‐4‐methylphenol), these compounds are distinct from those found in the defensive secretion of adult C. cordicollis. However, seven are more oxidized versions of the alkylphenolic compounds secreted by adult beetles: three hydroquinones (hydroquinone, methylhydroquinone and 2,3‐dimethylhydroquinone) and four quinones (p‐benzoquinone, toluquinone, 2,3‐dimethylquinone and ethyl‐p‐benzoquinone). An additional alkoxyphenol (2‐methoxy‐4‐ethylphenol) is also detected. Two patterns of composition are observed: in one, p‐benzoquinone and hydroquinone are undetectable and the ratio of toluquinone : 2,3‐dimethylquinone is 1 : 4.6 ± 0.6 (mean ± SE); in the other, all nine compounds are detectable and the ratio of toluquinone : 2,3‐dimethylquinone is 1 : 1.0 ± 0.2. These differences in pattern do not appear to be related to geographical source, sex or age of the larvae.     

Variation in economically and ecologically important traits in onion plant organs during reproductive development

The spatial distribution of organosulphur compounds throughout the onion (Allium cepa L.) plant body during reproduction is of ecological and horticultural interest. These secondary metabolites are associated with both pest resistance and many of the vegetable's culinary and medicinal properties, including the ability to inhibit platelet aggregation. Inhibition of platelet aggregation can be of benefit to human cardiovascular health. Organosulphur compound concentrations are associated with elemental sulphur, pungency, soluble solids and effect on human platelet aggregation. These parameters were evaluated in extracts collected separately from bulb scales, leaf blades, scapes and umbels biweekly throughout the reproductive phase of the life cycle of the onion. Significant variation in pungency, platelet inhibition, total sulphur content and soluble solids existed among samples of organs and within organs over time during reproductive growth. Furthermore, some extracts from leaf, scape and bulb induced rather than inhibited platelet aggregation.     

Larval habitat for the avian malaria vector Culex quinquefasciatus (Diptera: Culicidae) in altered mid‐elevation mesic‐dry forests in Hawai'i

Effective management of avian malaria (Plasmodium relictum) in Hawai'i's endemic honeycreepers (Drepanidinae) requires the identification and subsequent reduction or treatment of larval habitat for the mosquito vector, Culex quinquefasciatus (Diptera: Culicidae). We conducted ground surveys, treehole surveys, and helicopter aerial surveys from 2001–2003 to identify all potential larval mosquito habitat within two 100+ ha mesic‐dry forest study sites in Hawai'i Volcanoes National Park, Hawai'i; ‘Ainahou Ranch and Mauna Loa Strip Road. At ‘Ainahou Ranch, anthropogenic sites (43%) were more likely to contain mosquitoes than naturally occurring (8%) sites. Larvae of Cx. quinquefasciatus were predominately found in anthropogenic sites while Aedes albopictus larvae occurred less frequently in both anthropogenic sites and naturally‐occurring sites. Additionally, moderate‐size (≈20–22,000 liters) anthropogenic potential larval habitat had >50% probability of mosquito presence compared to larger‐ and smaller‐volume habitat (<50%). Less than 20% of trees surveyed at ‘Ainahou Ranch had treeholes and few mosquito larvae were detected. Aerial surveys at ‘Ainahou Ranch detected 56% (95% CI: 42–68%) of the potential larval habitat identified in ground surveys. At Mauna Loa Strip Road, Cx. quinquefasciatus larvae were only found in the rock holes of small intermittent stream drainages that made up 20% (5 of 25) of the total potential larval habitat. The volume of the potential larval habitat did not influence the probability of mosquito occurrence at Mauna Loa Strip Road. Our results suggest that Cx. quinquefasciatus abundance, and subsequently avian malaria, may be controlled by larval habitat reduction in the mesic‐dry landscapes of Hawai'i where anthropogenic sources predominate.     

Novel labdane diterpenoids from the aerial parts of Leonurus japonicus

Three new labdane diterpenoids, leojapones A–C (1–3), along with a new artifactual analogue (4) and four known terpenoids, were isolated from the EtOAc extract of the aerial parts of Leonurus japonicus Houtt. Their structures were elucidated by spectroscopic analyses and physicochemical evidences. The effects of new compounds against the abnormal increase in platelet aggregation induced by adenosine diphosphate were examined. But instead of inhibiting the abnormal platelet aggregation, compounds 1–3 boosted it significantly.     

Monitoring the early aggregatory behaviour and size of Aβ1-42 in the absence & presence of metal ions using dynamic light scattering

Background and aimAβ₁₋₄₂ is an amyloidogenic peptide found within senile plaques extracted from those who died with a diagnosis of Alzheimer’s disease. The potent neurotoxicity of this peptide is related to its propensity to form aggregated conformations in vivo, a process that is influenced by the species and concentration of metal ions present within the local environment. This study examines the impact of different metals upon the early aggregatory behaviour and size of Aβ₁₋₄₂ under simulated physiological conditions.MethodsThe size and aggregatory behaviour of Aβ₁₋₄₂ in the presence and absence of metal ions was monitored during the initial 30 min of fibril formation in real-time using dynamic light scattering.ResultsIntensity scattering measurements showed a clear tendency towards aggregation with regards to Aβ₁₋₄₂ only solutions (10 μM). Both equimolar Al³⁺ & Cu²⁺ lowered and stabilised the dimensions of Aβ₁₋₄₂ aggregates; however, a diminutive but significant increase in size was still observed over a 30-min period. While excess Al³⁺ continued to supress the size of Aβ_1−42, a 10-fold increase in the concentration of Cu²⁺ accelerated peptide aggregation relative to that observed for equimolar metal but not compared to Aβ₁₋₄₂ alone.ConclusionThese results infer that Al³⁺ ions stabilise and aid in the maintenance of smaller, toxic intermediates while excess Cu²⁺ facilitates the formation of larger, more inert, amorphous species exceeding 1 μm in size. Furthermore, we propose that metal-induced toxicity of Aβ₁₋₄₂ is reflective of their ability to preserve smaller oligomeric species in vitro.     

The path leading to the discovery of cadherin: In retrospect

Problems of adhesion between cells are undoubtedly one of the key major issues in developmental biology and its related field. It is little doubt that cell adhesion is one of the most fundamental mechanisms underlying the morphogenesis in multicellular animals and that it is intrinsically related to the metastasis of cancer cells as well. The historical source of adhesion studies can be traced to Wilson's work using sponges published in 1907. The present article starts to outline briefly the conceptual history up to a rise of cell adhesion in the 1950s as a problem for understanding morphogenesis in general. A crucial landmark to a recent burst of the interest to adhesion mechanisms in terms of adhesion molecules is the discovery of a group of major molecules functioning cell-to-cell adhesion, cadherins, from a research group at Kyoto University, Japan, which was initiated by myself and very successfully continued by Takeichi. A main part of the present review is to record the path leading to this important discovery based on my own personal experience, including some retrospective anecdotes. The path was initiated with a series of very simple experiments of a naïve question; that is, to examine whether or not different divalent cations were required for cell adhesion in qualitatively different manners.     

Oviposition aggregation pheromone in the Simulium damnosum complex

Abstract. Communal oviposition by the Simulium damnosum complex of Afrotropical blackflies (Diptera: Simuliidae) was investigated under controlled laboratory conditions, using wild-caught flies in Sierra Leone. Volatile compounds emitted by Simulium eggs were trapped using a closed collection system, and their attractiveness to gravid flies was tested in a two-choice behavioural bioassay. Significantly more female blackflies oviposited on substrates baited with freshly laid eggs (100% chose the baited substrate), or with the volatiles collected from freshly laid eggs (85% chose the baited substrate), in preference to the relevant control substrates. Substrates baited with volatiles from 12-h-old eggs were not significantly more attractive than controls (only 31% chose the baited substrates; P = 0.33). Gas chromatographic analysis of the egg volatiles consistently showed two peaks emanating from fresh eggs, but significantly lower amounts from 12-h-old eggs ( P <0.05). A novel system for collecting the volatiles from this and other blackfly species, as they laid eggs on a substrate in flowing water, is described. Volatiles collected using this method showed identical gas chromatographic profiles to those of fresh eggs alone, indicating that the flies themselves produced no other volatile chemical signals during oviposition. Evidently communal oviposition by S. damnosum s.l . was mediated by a pheromone emanating from fresh eggs. The role of pheromone-mediated egg aggregation in blackfly ecology is discussed, and its possible manipulation is considered.     

Root responses to legume plants integrate information on nitrogen availability and neighbour identity

Rhizobial symbiosis is known to increase the nitrogen availability in the rhizosphere of legumes. Therefore, it has been hypothesized that other plants’ roots should forage towards legume neighbours, but avoid non-legume neighbours. Yet, root distribution responding to legume plants as opposed to non-legumes has not yet been rigorously tested and might well be subject to integration of multiple environmental cues.In this study, wedevised an outdoor mesocosm experiment to examine root distributions of the two plant species Pilosella officinarum and Arenaria serpyllifolia in a two-factorial design. While one factor was ‘neighbour identity’, where plants were exposed to different legume or non-legume neighbours, the other factor was ‘nitrogen supply’. In the latter the nutrient-poor soil was supplemented with either nitrogen-free or with nitrogen-containing fertilizer.Unexpectedly, of all treatments that included a legume neighbour (eight different species or factor combinations), we found merely one case of root aggregation towards a legume neighbour (P. officinarum towards Medicago minima under nitrogen-fertilized conditions). In this very treatment, also P. officinarum root–shoot allocation was strongly increased, indicating that neighbour recognition is coupled with a contesting strategy.Considering the various response modes of the tested species towards the different legume and non-legume neighbours, we can conclude that roots integrate information on neighbour identity and resource availability in a complex manner. Especially the integration of neighbour identity in root decisions must be a vital aptitude for plants to cope with their complex biotic and abiotic environment in the field.     

A Novel Mechanism for NF-κB-activation via IκB-aggregation: Implications for Hepatic Mallory-Denk-Body Induced Inflammation

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Highlights

• •Liver Mallory-Denk-Body inducers elicited an IκBα-loss and NF-κB-activation.
• •IκBα-loss was due to its sequestration into insoluble cytoplasmic aggregates.
• •Four proteomic approaches identified 10 IκBα-interacting/aggregating proteins.
• •Nup153/RanBP2-aggregation prevented IκBα nuclear entry for ending NF-κB-activation.