The functional role of temperate forest understorey vegetation in a changing world

Temperate forests cover 16% of the global forest area. Within these forests, the understorey is an important biodiversity reservoir that can influence ecosystem processes and functions in multiple ways. However, we still lack a thorough understanding of the relative importance of the understorey for temperate forest functioning. As a result, understoreys are often ignored during assessments of forest functioning and changes thereof under global change. We here compiled studies that quantify the relative importance of the understorey for temperate forest functioning, focussing on litter production, nutrient cycling, evapotranspiration, tree regeneration, pollination and pathogen dynamics. We describe the mechanisms driving understorey functioning and develop a conceptual framework synthesizing possible effects of multiple global change drivers on understorey-mediated forest ecosystem functioning. Our review illustrates that the understorey's contribution to temperate forest functioning is significant but varies depending on the ecosystem function and the environmental context, and more importantly, the characteristics of the overstorey. To predict changes in understorey functioning and its relative importance for temperate forest functioning under global change, we argue that a simultaneous investigation of both overstorey and understorey functional responses to global change will be crucial. Our review shows that such studies are still very scarce, only available for a limited set of ecosystem functions and limited to quantification, providing little data to forecast functional responses to global change

Elucidation of the Mode of Action of a New Antibacterial Compound Active against Staphylococcus aureus and Pseudomonas aeruginosa.

Nosocomial and community-acquired infections caused by multidrug resistant bacteria represent a major human health problem. Thus, there is an urgent need for the development of antibiotics with new modes of action. In this study, we investigated the antibacterial characteristics and mode of action of a new antimicrobial compound, SPI031 (N-alkylated 3, 6-dihalogenocarbazol 1-(sec-butylamino)-3-(3,6-dichloro-9H-carbazol-9-yl)propan-2-ol), which was previously identified in our group. This compound exhibits broad-spectrum antibacterial activity, including activity against the human pathogens Staphylococcus aureus and Pseudomonas aeruginosa. We found that SPI031 has rapid bactericidal activity (7-log reduction within 30 min at 4x MIC) and that the frequency of resistance development against SPI031 is low. To elucidate the mode of action of SPI031, we performed a macromolecular synthesis assay, which showed that SPI031 causes non-specific inhibition of macromolecular biosynthesis pathways. Liposome leakage and membrane permeability studies revealed that SPI031 rapidly exerts membrane damage, which is likely the primary cause of its antibacterial activity. These findings were supported by a mutational analysis of SPI031-resistant mutants, a transcriptome analysis and the identification of transposon mutants with altered sensitivity to the compound. In conclusion, our results show that SPI031 exerts its antimicrobial activity by causing membrane damage, making it an interesting starting point for the development of new antibacterial therapies

Modelling the treated course of schizophrenia: development of a discrete event simulation model

In schizophrenia, modelling techniques may be needed to estimate the long-term costs and effects of new interventions. However, it seems that a simple direct link between symptoms and costs does not exist. Decisions about whether a patient will be hospitalized or admitted to a different healthcare setting are based not only on symptoms but also on social and environmental factors. This paper describes the development of a model to assess the dependencies between a broad range of parameters in the treatment of schizophrenia. In particular, the model attempts to incorporate social and environmental factors into the decision-making process for the prescription of new drugs to patients. The model was used to analyse the potential benefits of improving compliance with medication by 20% in patients in the UK. A discrete event simulation (DES) model was developed, to describe a cohort of schizophrenia patients with multiple psychotic episodes. The model takes into account the patient's sex, disease severity, potential risk of harm to self and society, and social and environmental factors. Other variables that change over time include the number of psychiatric consultations, the presence of psychotic episodes, symptoms, treatments, compliance, side-effects, the lack of ability to take care of him/herself, care setting and risk of harm. Outcomes are costs, psychotic episodes and symptoms. Univariate and multivariate sensitivity analyses were performed. Direct medical costs were considered (year of costing 2002), applying a 6.0% discount rate for costs and a 1.5% discount rate for outcome. The timeframe of the model is 5 years. When 50% of the decisions about the patient care setting are based on symptoms, a 20% increase in compliance was estimated to save £16 147 and to avoid 0.55 psychotic episodes per patient over 5 years. Sensitivity analysis showed that the costs savings associated with increased compliance are robust over a range of variations in parameters. DES offers a flexible structure for modelling a disease, taking into account how a patient's history affects the course of the disease over time. This approach is particularly pertinent to schizophrenia, in which treatment decisions are complex. The model shows that better compliance increases the time between relapses, decreases the symptom score, and reduces the requirement for treatment in an intensive patient care setting, leading to cost savings. The extent of the cost savings depends on the relative importance of symptoms and of social and environmental factors in these decisions