Accumulation and detoxication responses of the gastropod Lymnaea stagnalis to single and combined exposures to natural (cyanobacteria) and anthropogenic (the herbicide RoundUp® Flash) stressors.

Freshwater gastropods are increasingly exposed to multiple stressors in the field such as the herbicide glyphosate in Roundup formulations and cyanobacterial blooms either producing or not producing microcystins (MCs), potentially leading to interacting effects. Here, the responses of Lymnaea stagnalis to a 21-day exposure to non-MC or MC-producing (33μgL−1) Planktothrix agardhii alone or in combination with the commercial formulation RoundUp®Flash at a concentration of 1μgL−1glyphosate, followed by 14days of depuration, were studied via i) accumulation of free and bound MCs in tissues, and ii) activities of anti-oxidant (catalase CAT) and biotransformation (glutathione-S-transferase GST) enzymes. During the intoxication, the cyanobacterial exposure induced an early increase of CAT activity, independently of the MC content, probably related to the production of secondary cyanobacterial metabolites. The GST activity was induced by RoundUp®Flash alone or in combination with non MC-producing cyanobacteria, but was inhibited by MC-producing cyanobacteria with or without RoundUp®Flash. Moreover, MC accumulation in L. stagnalis was 3.2 times increased when snails were concomitantly exposed to MC-producing cyanobacteria with RoundUp®, suggesting interacting effects of MCs on biotransformation processes. The potent inhibition of detoxication systems by MCs and RoundUp®Flash was reversible during the depuration, during which CAT and GST activities were significantly higher in snails previously exposed to MC-producing cyanobacteria with or without RoundUp®Flash than in other conditions, probably related to the oxidative stress caused by accumulated MCs remaining in tissues

Cross talk: two way allelopathic interactions between toxic Microcystis and Daphnia.

Due to eutrophication, freshwater ecosystems frequently experience cyanobacterial blooms, many of which produce bioactive metabolites that can affect vertebrates and invertebrates life traits. Zooplankton are able to develop tolerance as a physiological response to cyanobacteria and their bioactive compounds, however, this comes with energetic cost that in turn influence Daphnia life traits and may impair populations. Vice versa, it has been suggested that Daphnia are able to reduce cyanobacterial dominance until a certain cyanobacterial density; it remains unclear whether Daphnia metabolites alone influence the physiological state and bioactive metabolites production of cyanobacteria. Hence, this study investigates mutual physiological reactions of toxic Microcystis aeruginosa PCC7806 and Daphnia magna. We hypothesize that a) the presence of D. magna will negatively affect growth, increase stress response and metabolites production in M. aeruginosa PCC7806 and b) the presence of M. aeruginosa PCC7806 will negatively affect physiological responses and life traits in D. magna. In order to test these hypotheses experiments were conducted in a specially designed co-culture chamber that allows exchange of the metabolites without direct contact. A clear mutual impact was evidenced. Cyanobacterial metabolites reduced survival of D.magna and decreased oxidative stress enzyme activity. Simultaneously, presence of D.magna did not affect photosynthetic activity. However, ROS increase and tendencies in cell density decrease were observed on the same day, suggesting possible energy allocation towards anti-oxidative stress enzymes, or other protection mechanisms against Daphnia infochemicals, as the strain managed to recover. Elevated concentration of intracellular and overall extracellular microcystin MC-LR, as well as intracellular concentrations of aerucyclamide A and D in the presence of Daphnia, indicating a potential protective or anti-grazing function. However, more research is needed to confirm these findings

Efficacy of antifungal agents against fungal spores: an in vitro study using microplate laser nephelometry and an artificially infected 3D skin model

Dermal fungal infections seem to have increased over recent years. There is further a shift from anthropophilic dermatophytes to a growing prevalence of zoophilic species and the emergence of resistant strains. New antifungals are needed to combat these fungi and their resting spores. This study aimed to investigate the sporicidal effects of sertaconazole nitrate using microplate laser nephelometry against the microconidia of Trichophyton , chlamydospores of Epidermophyton , blastospores of Candida , and conidia of the mold Scopulariopsis brevicaulis . The results obtained were compared with those from ciclopirox olamine and terbinafine. The sporicidal activity was further determined using infected three‐dimensional full skin models to determine the antifungal effects in the presence of human cells. Sertaconazole nitrate inhibited the growth of dermatophytes, molds, and yeasts. Ciclopirox olamine also had good antifungal activity, although higher concentrations were needed compared to sertaconazole nitrate. Terbinafine was highly effective against most dermatophytes, but higher concentrations were required to kill the resistant strain Trichophyton indotineae . Sertaconazole nitrate, ciclopirox olamine, and terbinafine had no negative effects on full skin models. Sertaconazole nitrate reduced the growth of fungal and yeast spores over 72 h. Ciclopirox olamine and terbinafine also inhibited the growth of dermatophytes and molds but had significantly lower effects on the yeast. Sertaconazole nitrate might have advantages over the commonly used antifungals ciclopirox olamine and terbinafine in combating resting spores, which persist in the tissues, and thus in the therapy of recurring dermatomycoses

Towards an integrated ecological-economic land-use change model

Land-use changes have transformed tropical landscapes throughout the past decades dramatically. We describe here an ecologicaleconomicland-use change model to provide an integrated, exploratory tool to analyze how tropical land use and land-use change affect ecological and socio-conomic functions. The guiding question of the model is what kind of landscape mosaic can improve the ensemble of ecosystem functioning, biodiversity and economic benefit based on the synergies and trade-offs that we have to account for. The economic submodel simulates smallholder land-use management decisions based on a profit maximization assumption and a Leontief production function. Each household determines factor inputs for all household fields and decides about land-use change based on available wealth. The ecological submodel includes a simple account of carbon sequestration in above- and belowground vegetation. Initialized with realistic or artificial land use maps, the ecological-economic model will advance our understanding of the mechanisms underlying the trade-offs and synergies of ecological and economic functions in tropical landscapes

Cell free Microcystis aeruginosa spent medium affects Daphnia magna survival and stress response.

Primary consumers in freshwater ecosystems, such as the zooplankton organism Daphnia magna, are highly affected by cyanobacteria, both as they may use it as a food source but also by cyanobacterial metabolites present in the water. Here, we investigate the impacts of cyanobacterial metabolites focussing on the environmental realistic scenario of the naturally released mixture without crushing cyanobacterial cells or their uptake as food. Therefore, D. magna were exposed to two concentrations of cell free cyanobacterial spent medium from Microcystis aeruginosa PCC 7806 to represent higher and lower ecologically-relevant concentrations of cyanobacterial metabolites. Including microcystin-LR, 11 metabolites have been detected of which 5 were quantified. Hypothesising concentration and time dependent negative impact, survival, gene expression marking digestion and metabolism, oxidative stress response, cell cycle and molting as well as activities of detoxification and antioxidant enzymes were followed for 7 days. D. magna suffered from oxidative stress as both catalase and glutathione S-transferase enzyme activities significantly decreased, suggesting enzyme exhaustibility after 3 and 7 days. Moreover, gene-expressions of the 4 stress markers (glutathione S-transferase, glutathione peroxidase, catalase and thioredoxin) were merely downregulated after 7 days of exposure. Energy allocation (expression of glyceraldehyde-3-phosphate dehydrogenase) was increased after 3 days but decreased as well after 7 days exposure. Cell cycle was impacted time dependently but differently by the two concentrations, along with an increasing downregulation of myosin heavy chain responsible for cell arrangement and muscular movements. Deregulation of nuclear hormone receptor genes indicate that D. magna hormonal steering including molting seemed impaired despite no detection of microviridin J in the extracts. As a consequence of all those responses and presumably of more than investigated molecular and physiological changes, D. magna survival was impaired over time, in a concentration dependent manner. Our results confirm that besides microcystin-LR, other secondary metabolites contribute to negative impact on D. magna survival and stress response

Daphnia magna exudates impact physiological and metabolic changes in microcystis aeruginosa.

While the intracellular function of many toxic and bioactive cyanobacterial metabolites is not yet known, microcystins have been suggested to have a protective role in the cyanobacterial metabolism, giving advantage to toxic over nontoxic strains under stress conditions. The zooplankton grazer Daphnia reduce cyanobacterial dominance until a certain density, which may be supported by Daphnia exudates, affecting the cyanobacterial physiological state and metabolites’ production. Therefore, we hypothesized that D. magna spent medium will impact the production of cyanobacterial bioactive metabolites and affect cyanobacterial photosynthetic activity in the nontoxic, but not the toxic strain. Microcystin (MC-LR and des-MC-LR) producing M. aeruginosa PCC7806 and its non-microcystin producing mutant were exposed to spent media of different D. magna densities and culture durations. D. magna spent medium of the highest density (200/L) cultivated for the shortest time (24 h) provoked the strongest effect. D.magna spent medium negatively impacted the photosynthetic activity of M. aeruginosa PCC7806, as well as the dynamics of intracellular and extracellular cyanobacterial metabolites, while its mutant was unaffected. In the presence of Daphnia medium, microcystin does not appear to have a protective role for the strain. On the contrary, extracellular cyanopeptolin A increased in M. aeruginosa PCC7806 although the potential anti-grazing role of this compound would require further studies

A Structured, Manual-Based Low-Level Intervention vs. Treatment as Usual Evaluated in a Randomized Controlled Trial for Adolescents with Extreme Obesity - the STEREO Trial

Background: To compare efficacy and safety of a manual-based low-level psychological intervention with treatment as usual (weight loss treatment). Methods: A two-armed randomized controlled trial without blinding and computer-based stratified block randomization included adolescents and young adults (14.0-24.9 years) with a BMI ≥ 30 kg/m2 at five German university hospitals. Primary outcomes were adherence (participation rate ≥ 5/6 sessions) and quality of life (DISABKIDS-37) 6 months after randomization. Secondary outcomes included depression, self-esteem, and perceived stress scores. Results: Of 397 screened adolescents, 119 (mean BMI 40.4 ± 7.0 kg/m2, 49.6% female) were randomized to the manual-based low-level intervention (n = 59) or treatment as usual (n = 60). We observed no group difference for adherence (absolute risk reduction 0.4%, 95% CI -14.7% to 15.5%; p = 1.0) or health- related quality of life (score difference 8.1, 95% CI -2.1 to 18.3; p = 0.11). Among all secondary outcomes, we detected explorative evidence for an effect on the DISABKIDS-37 ‘social exclusion' subscale (score difference 15.5; 95% CI 1.6-29.4; p = 0.03). 18/19 adverse events occurred in 26 participants, none were classified as serious. Conclusion: Adherence to a coping-oriented intervention was comparable to weight loss treatment, although it was weak in both interventions. Psychological interventions may help to overcome social isolation; further confirmation is required

Changes in the Frontotemporal Cortex and Cognitive Correlates in First-Episode Psychosis

Background: Loss of cortical volume in frontotemporal regions has been reported in patients with schizophrenia and their relatives. Cortical area and thickness are determined by different genetic processes, and measuring these parameters separately may clarify disturbances in corticogenesis relevant to schizophrenia. Our study also explored clinical and cognitive correlates of these parameters.Methods: Thirty-seven patients with first-episode psychosis (34 schizophrenia, 3 schizoaffective disorder) and 38 healthy control subjects matched for age and sex took part in the study. Imaging was performed on an magnetic resonance imaging 1.5-T scanner. Area and thickness of the frontotemporal cortex were measured using a surface-based morphometry method (Freesurfer). All subjects underwent neuropsychologic testing that included measures of premorbid and current IQ, working and verbal memory, and executive function.Results: Reductions in cortical area, more marked in the temporal cortex, were present in patients. Overall frontotemporal cortical thickness did not differ between groups, although regional thinning of the right superior temporal region was observed in patients. There was a significant association of both premorbid IQ and IQ at disease onset with area, but not thickness, of the frontotemporal cortex, and working memory span was associated with area of the frontal cortex. These associations remained significant when only patients with schizophrenia were considered.Conclusions: Our results suggest an early disruption of corticogenesis in schizophrenia, although the effect of subsequent environmental factors cannot be excluded. In addition, cortical abnormalities are subject to regional variations and differ from those present in neurodegenerative diseases

A Common Variant of PNPLA3 (p.I148M) Is Not Associated with Alcoholic Chronic Pancreatitis

Contains fulltext : 110441.pdf (publisher's version ) (Open Access)BACKGROUND: Chronic pancreatitis (CP) is an inflammatory disease that in some patients leads to exocrine and endocrine dysfunction. In industrialized countries the most common aetiology is chronic alcohol abuse. Descriptions of associated genetic alterations in alcoholic CP are rare. However, a common PNPLA3 variant (p.I148M) is associated with the development of alcoholic liver cirrhosis (ALC). Since, alcoholic CP and ALC share the same aetiology PNPLA3 variant (p.I148M) possibly influences the development of alcoholic CP. METHODS: Using melting curve analysis we genotyped the variant in 1510 patients with pancreatitis or liver disease (961 German and Dutch alcoholic CP patients, 414 German patients with idiopathic or hereditary CP, and 135 patients with ALC). In addition, we included in total 2781 healthy controls in the study. RESULTS: The previously published overrepresentation of GG-genotype was replicated in our cohort of ALC (p-value <0.0001, OR 2.3, 95% CI 1.6-3.3). Distributions of genotype and allele frequencies of the p.I148M variant were comparable in patients with alcoholic CP, idiopathic and hereditary CP and in healthy controls. CONCLUSIONS: The absence of an association of PNPLA3 p.I148M with alcoholic CP seems not to point to a common pathway in the development of alcoholic CP and alcoholic liver cirrhosis