Botanical drugs, synergy, and network pharmacology: forth and back to intelligent mixtures

For centuries the science of pharmacognosy has dominated rational drug development until it was gradually substituted by target-based drug discovery in the last fifty years. Pharmacognosy stems from the different systems of traditional herbal medicine and its "reverse pharmacology" approach has led to the discovery of numerous pharmacologically active molecules and drug leads for humankind. But do botanical drugs also provide effective mixtures? Nature has evolved distinct strategies to modulate biological processes, either by selectively targeting biological macromolecules or by creating molecular promiscuity or polypharmacology (one molecule binds to different targets). Widely claimed to be superior over monosubstances, mixtures of bioactive compounds in botanical drugs allegedly exert synergistic therapeutic effects. Despite evolutionary clues to molecular synergism in nature, sound experimental data are still widely lacking to support this assumption. In this short review, the emerging concept of network pharmacology is highlighted, and the importance of studying ligand-target networks for botanical drugs is emphasized. Furthermore, problems associated with studying mixtures of molecules with distinctly different pharmacodynamic properties are addressed. It is concluded that a better understanding of the polypharmacology and potential network pharmacology of botanical drugs is fundamental in the ongoing rationalization of phytotherapy.

Reverse-translational biomarker validation of Abnormal Repetitive Behaviors in mice: an illustration of the 4P's modeling approach

The NIMH's new strategic plan, with its emphasis on the "4P's" (Prediction, Pre-emption, Personalization, and Populations) and biomarker-based medicine requires a radical shift in animal modeling methodology. In particular 4P's models will be non-determinant (i.e. disease severity will depend on secondary environmental and genetic factors); and validated by reverse-translation of animal homologues to human biomarkers. A powerful consequence of the biomarker approach is that different closely related disorders have a unique fingerprint of biomarkers. Animals can be validated as a highly specific model of a single disorder by matching this 'fingerprint'; or as a model of a symptom seen in multiple disorders by matching common biomarkers. Here we illustrate this approach with two Abnormal Repetitive Behaviors (ARBs) in mice: stereotypies and barbering (hair pulling). We developed animal versions of the neuropsychological biomarkers that distinguish human ARBs, and tested the fingerprint of the different mouse ARBs. As predicted, the two mouse ARBs were associated with different biomarkers. Both barbering and stereotypy could be discounted as models of OCD (even though they are widely used as such), due to the absence of limbic biomarkers which are characteristic of OCD and hence are necessary for a valid model. Conversely barbering matched the fingerprint of trichotillomania (i.e. selective deficits in set-shifting), suggesting it may be a highly specific model of this disorder. In contrast stereotypies were correlated only with a biomarker (deficits in response shifting) correlated with stereotypies in multiple disorders, suggesting that animal stereotypies model stereotypies in multiple disorders.

Der öffentliche Vertrieb von kollektiven Kapitalanlagen - Illustration am Beispiel des vertraglichen Anlagefonds

Der vorliegende Beitrag befasst sich mit der rechtlichen Analyse des im Recht der kollektiven Kapitalanlagen geregelten Fondsvertriebs aus aufsichts- und privatrechtlicher Sicht. Es werden dabei die Rahmenbedingungen des Vertriebs anhand der wichtigsten kollektiven Kapitalanlage, des vertraglichen Anlagefonds, aufgezeigt. Beim Direktvertrieb und beim Vertrieb durch Dritte besteht ein Geflecht von gewerbepolizeilichen Vorschriften und privatrechtlichen Normen, die von den involvierten Parteien beachtet werden müssen. Der Fokus des Beitrags liegt deshalb sowohl auf der gewerbepolizeilichen Aufsicht über die kollektiven Kapitalanlagen als auch auf den (vertraglichen) Rechtsbeziehungen zwischen den Anbietern von kollektiven Kapitalanlagen und deren Erfüllungsgehilfen einerseits und den Anlegern andererseits. Entsprechend der Behandlung des Themas in dieser Zeitschrift werden auch die Grundlagen der kollektiven Kapitalanlagen dargestellt.

Drivers of collaboration to mitigate climate change: An illustration of Swiss climate policy over 15 years

Climate change mitigation policy is driven by scientific knowledge and involves actors from the international, national and local decision-making levels. This multi-level and cross-sectoral context requires collaborative management when designing mitigation solutions over time and space. But collaboration in general policymaking settings, and particularly in the complex domain of climate mitigation, is not an easy task. This paper addresses the question of what drives collaboration among collective actors involved in climate mitigation policy. We wish to investigate whether common beliefs or power structures influence collaboration among actors. We adopt a longitudinal approach to grasp differences between the early and more advanced stages of mitigation policy design. We use survey data to investigate actors’ collaboration, beliefs and power, and apply a Stochastic Actor-oriented Model for network dynamics to three subsequent networks in Swiss climate policy between 1995 and 2012. Results show that common beliefs among actors, as well as formal power structures, have a higher impact on collaboration relations than perceived power structures. Furthermore, those effects hold true for decision-making about initial mitigation strategies, but less so for the implementation of those measures.

Non-naturalized alien plants receive fewer flower visits than naturalized and native plants in a Swiss botanical garden

Many animal-pollinated plant species have been introduced to non-native regions without their usual pollinators. Nevertheless, some of these alien species managed to establish reproducing naturalized populations, which might negatively affect native plants. Recent studies have shown that many naturalized alien species can readily attract native pollinators. However, it is not known whether alien species that have not established naturalized populations are less successful in attracting pollinators. Therefore, we tested whether flower-visitation rates are lower for non-naturalized aliens than for naturalized alien and native species. We conducted a comparative study on flower visitation of 185 native, 37 naturalized alien and 224 non-naturalized alien plant species in the Botanical Garden of Bern, Switzerland. Our phylogenetically corrected analyses showed that non-naturalized alien species received fewer flower visitors than both naturalized alien and native species. Native, naturalized alien and non-naturalized alien species were visited by similar flower-visitor communities. Furthermore, among the naturalized alien species, the ones with a broader distribution range in Switzerland received a more diverse set of flower visitors. Although it has been suggested that most alien plants can readily integrate into native plant–pollinator networks, we show evidence that the capacity to attract flower visitors in non-native regions is different for naturalized and non-naturalized alien plants. Therefore, we conclude that successful naturalization of alien plants may be related to flower visitation.

Ein Update zur "Neuropsychotherapie" und Illustration aus der laufenden Forschung zum Einsatz emotionsfokussierter Vorgehensweisen

Während es fast trivial erscheint, dass erfolgreiche Psychotherapien – also Veränderungen im Erleben und Verhalten – prinzipiell mit funktionellen und strukturellen Veränderungen des Gehirns zusammenhängen, erweist es sich als deutlich anspruchsvoller, spezifischeren Fragestellungen nachzugehen und aus ihnen Implikationen für die Psychotherapie zu abzuleiten: Welche neuronalen Mechanismen sind an psychotherapeutisch relevanten Veränderungen im Erleben und Verhalten beteiligt? Wodurch werden diese neuronalen Wirkmechanismen beeinflusst? Und wie werden diese Erkenntnisse für die Psychotherapie praktisch nutzbar gemacht? Anhand aktueller Forschungsbefunde und konzeptueller Überlegungen in Anlehnung an Grawes “Neuropsychotherapie” wird in diesem Beitrag zu solchen und verwandten Fragen Stellung genommen. Eine laufende Studie an der Schnittstelle zwischen Psychotherapieprozessforschung und Neurowissenschaften illustriert, wie neuronale Wirkmechanismen erforscht und in bestehende psychologisch-psychotherapeutische Theorien eingebunden werden können. Untersucht werden hierbei die Effekte einer emotionsfokussierten Mikrointervention auf das subjektive emotionale Erleben und neurophysiologische Parameter. Solche neuronalen korrelate emotionaler Veränderungsprozesse werden vor dem theoretischen Hintergrund emotionsfokussierter und allgemeiner Psychotherapie interpretiert.

Model for ranking freshwater fish farms according to their risk of infection and illustration for viral haemorrhagic septicaemia

We developed a model to calculate a quantitative risk score for individual aquaculture sites. The score indicates the risk of the site being infected with a specific fish pathogen (viral haemorrhagic septicaemia virus (VHSV); infectious haematopoietic necrosis virus, Koi herpes virus), and is intended to be used for risk ranking sites to support surveillance for demonstration of zone or member state freedom from these pathogens. The inputs to the model include a range of quantitative and qualitative estimates of risk factors organised into five risk themes (1) Live fish and egg movements; (2) Exposure via water; (3) On-site processing; (4) Short-distance mechanical transmission; (5) Distance-independent mechanical transmission. The calculated risk score for an individual aquaculture site is a value between zero and one and is intended to indicate the risk of a site relative to the risk of other sites (thereby allowing ranking). The model was applied to evaluate 76 rainbow trout farms in 3 countries (42 from England, 32 from Italy and 2 from Switzerland) with the aim to establish their risk of being infected with VHSV. Risk scores for farms in England and Italy showed great variation, clearly enabling ranking. Scores ranged from 0.002 to 0.254 (mean score 0.080) in England and 0.011 to 0.778 (mean of 0.130) for Italy, reflecting the diversity of infection status of farms in these countries. Requirements for broader application of the model are discussed. Cost efficient farm data collection is important to realise the benefits from a risk-based approach.