•Challenges for smart intensification of marginal land are manifold•Tools for precise agriculture will aid to detect pollutant hotspots and poor soils•Crop rotation and adapted crop choice will yield ...biomass•Amendments will sequester carbon and release fertilizer when needed•Potentials of marginal soils can be unlocked and lead to ecological and economical success
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The rapid increase of the world population constantly demands more food production from agricultural soils. This causes conflicts, since at the same time strong interest arises on novel bio-based products from agriculture, and new perspectives for rural landscapes with their valuable ecosystem services. Agriculture is in transition to fulfill these demands. In many countries, conventional farming, influenced by post-war food requirements, has largely been transformed into integrated and sustainable farming. However, since it is estimated that agricultural production systems will have to produce food for a global population that might amount to 9.1 billion by 2050 and over 10 billion by the end of the century, we will require an even smarter use of the available land, including fallow and derelict sites. One of the biggest challenges is to reverse non-sustainable management and land degradation. Innovative technologies and principles have to be applied to characterize marginal lands, explore options for remediation and re-establish productivity. With view to the heterogeneity of agricultural lands, it is more than logical to apply specific crop management and production practices according to soil conditions. Cross-fertilizing with conservation agriculture, such a novel approach will provide (1) increased resource use efficiency by producing more with less (ensuring food security), (2) improved product quality, (3) ameliorated nutritional status in food and feed products, (4) increased sustainability, (5) product traceability and (6) minimized negative environmental impacts notably on biodiversity and ecological functions. A sustainable strategy for future agriculture should concentrate on production of food and fodder, before utilizing bulk fractions for emerging bio-based products and convert residual stage products to compost, biochar and bioenergy. The present position paper discusses recent developments to indicate how to unlock the potentials of marginal land.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
(2S,3R,4R,5S,6R)-2-(3-(4-Ethoxybenzyl)-4-chlorophenyl)-6-hydroxymethyl-tetrahydro-2H-pyran-3,4,5-triol (dapagliflozin; BMS-512148) is a potent sodium-glucose cotransporter type II inhibitor in ...animals and humans and is currently under development for the treatment of type 2 diabetes. The preclinical characterization of dapagliflozin, to allow compound selection and prediction of pharmacological and dispositional behavior in the clinic, involved Caco-2 cell permeability studies, cytochrome P450 (P450) inhibition and induction studies, P450 reaction phenotyping, metabolite identification in hepatocytes, and pharmacokinetics in rats, dogs, and monkeys. Dapagliflozin was found to have good permeability across Caco-2 cell membranes. It was found to be a substrate for P-glycoprotein (P-gp) but not a significant P-gp inhibitor. Dapagliflozin was not found to be an inhibitor or an inducer of human P450 enzymes. The in vitro metabolic profiles of dapagliflozin after incubation with hepatocytes from mice, rats, dogs, monkeys, and humans were qualitatively similar. Rat hepatocyte incubations showed the highest turnover, and dapagliflozin was most stable in human hepatocytes. Prominent in vitro metabolic pathways observed were glucuronidation, hydroxylation, and O-deethylation. Pharmacokinetic parameters for dapagliflozin in preclinical species revealed a compound with adequate oral exposure, clearance, and elimination half-life, consistent with the potential for single daily dosing in humans. The pharmacokinetics in humans after a single dose of 50 mg of (14)Cdapagliflozin showed good exposure, low clearance, adequate half-life, and no metabolites with significant pharmacological activity or toxicological concern.
Background Anodal transcranial direct current stimulation (tDCS) of the prefrontal cortex has been proposed as therapeutic intervention in major depression. According to clinical needs, this study ...addresses the question whether tDCS is effective in treatment resistant major depressive episodes. Methods Twenty-two patients with a major depressive episode were randomly assigned to a cross-over protocol comparing tDCS and placebo stimulation add-on to a stable antidepressant medication. The parameters of active tDCS were: 1 or 2 mA for 20 minutes/day, anode over the left dorsolateral prefrontal cortex, cathode over the contralateral supraorbital region. Active and placebo tDCS was applied for 2 weeks using indistinguishable DC stimulators. Patients, raters, and operators were blinded to treatment conditions. Results There was no significant difference in depression scores after 2 weeks of real compared with 2 weeks of sham tDCS. Scores on the Hamilton Depression Rating Scale were reduced from baseline by 14.7% for active tDCS and 10% for placebo tDCS. In contrast, subjective mood ratings showed an increase in positive emotions after real tDCS compared with sham tDCS. Conclusions Anodal tDCS, applied for 2 weeks, was not superior to placebo treatment in patients with treatment resistant depression. However, secondary outcome measures are pointing to a positive effect of tDCS on emotions. Therefore, modified and improved tDCS protocols should be carried out in controlled pilot trials to develop tDCS towards an efficacious antidepressant intervention in therapy-resistant depression.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Summary Chronic hepatitis E has been described several times in strongly immunosuppressed HIV-patients. We describe the persistence of HEV-infection in an HIV-patient despite a restored immune ...response. This case demonstrates that HEV-infection can persist in formerly immunosuppressed individuals irrespective of the current immune status. Persisting HEV-infection can lead to chronic inflammation and liver cirrhosis. Physicians should be aware of the possibility of chronic hepatitis E even in patients that are not any longer immunocompromised. However, ribavirin is an efficient treatment option.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Summary
Acute hepatitis C virus infection remains a major health concern in human immunodeficiency virus(HIV)‐infected men who have sex with men (MSM). New direct‐acting antiviral agent (DAA) ...combination therapy has not yet been approved for the treatment for acute hepatitis C virus(HCV), thereby potentially causing deferral of HCV treatment. Therefore, we aimed to study the course of liver disease after an episode of acute HCV. This study is a retrospective single‐centre cohort of HIV‐positive MSM with acute HCV infection. Liver fibrosis was estimated by Fibroscan® and Fibrotest®. Liver‐related and non‐liver‐related outcomes were documented. Overall 213 episodes of acute HCV infection in 178 men were documented. Median follow‐up for all included patients was 38.7 months. Spontaneous HCV clearance was found in 10.8% of patients, which was significantly associated with older age, lower HCV RNA levels, and higher ALT levels upon initial acute HCV diagnosis. Treatment with interferon‐based therapy was initiated in 86.3% of cases, resulting in a sustained virological response(SVR) rate of 70.7%. After 3 years’ follow‐up, significant liver fibrosis of METAVIR F2 stage or higher was found in 39.4% of patients after first acute HCV diagnosis. Higher age, physician‐declared alcoholism, and nonresponse to acute HCV therapy were independently associated with higher fibrosis stages. Ten patients died during the observation period (IR 1.4/100 patient‐years) and four during interferon treatment. Significant liver fibrosis is a common finding in HIV‐positive MSM following acute HCV infection despite high treatment uptake and cure rates, suggesting the need for close liver disease monitoring particularly if HCV treatment is deferred.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
The ever-growing spread of resistance in medicine and agriculture highlights the need to identify new antimicrobials. Microbial volatile organic compounds (VOCs) are one of the most promising groups ...of chemicals to meet this need. These rarely exploited molecules exhibit antimicrobial activity and their high vapour pressure makes them ideal for application in surface sterilisation, and in particular, in biofumigation. Therefore, we adapted the previously developed Two Clamp VOCs Assay (TCVA) to a new high-throughput screening for the detection of novel antifungal VOCs from metagenomic clone libraries. As a proof of concept, we tested the new high-throughput TCVA (htTCVA) by sourcing a moss metagenomic library against Fusarium culmorum. This led to the identification of five clones that inhibited the growth of mycelium and spores in vitro by up to 8% and 30% and subsequently, to the identification of VOCs that are potentially, and in part responsible for the clones’ antifungal activity. For these VOCs, the in vitro effect of the pure compounds was as high as 100%. These results demonstrate the robustness and feasibility of the htTCVA, which provides access to completely new and unexplored biosynthetic pathways and their secondary metabolites.
•In this article we highlight the biotechnological potential of microbial communities living in plants.•Several examples give evidence for the vast diversity of metabolites and enzymes that can be ...discovered in plant-microbiomes.•We summarize findings from plant-metagenomics, which serve as a tool for the exploration of structural and functional diversity.
There is growing demand for new bioactive compounds and biologicals for the pharmaceutical, agro- and food industries. Plant-associated microbes present an attractive and promising source to this end, but are nearly unexploited. Therefore, bioprospecting of plant microbiomes is gaining more and more attention. Due to their highly specialized and co-evolved genetic pool, plant microbiomes host a rich secondary metabolism. This article highlights the potential detection and use of secondary metabolites and enzymes derived from plant-associated microorganisms in biotechnology. As an example we summarize the findings from the moss microbiome with special focus on the genus Sphagnum and its biotechnological potential for the discovery of novel microorganisms and bioactive molecules. The selected examples illustrate unique and yet untapped properties of plant-associated microbiomes, which are an immense treasure box for future research.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Projected population growth and climate change will make it inevitable to convert neglected and marginal land into productive arable land. We investigate the influence of agricultural management ...practices on nutrient stocks and soil functions during the conversion of former extensively used grassland to arable land. Effects of grassland removal, tillage, intercropping with faba bean (Vicia faba) and its later incorporation were studied with respect to soil properties and bacterial community structure. Therefore, composite samples were collected with a core sampler from the topsoil (0–20 cm) in (a) the initial grassland, (b) the transitional phase during the vegetation period of V. faba, (c) after ploughing the legume in, and (d) untreated controls. In all samples, nitrate-N, ammonium-N, dissolved organic carbon (DOC) and total nitrogen bound (TNb) were analyzed and comparisons of the bacterial community structure after 16S-amplicon sequencing were performed to assess soil functions. Mineralization after grassland conversion followed by the biological nitrogen fixation of broad beans enhanced the nitrate-N content in bulk soil from 4 to almost 50 μg N g−1dw. Bacterial community structure on phylum level in bulk soil was dominated by Proteobacteria, Actinobacteria, Acidobacteria, Chloroflexi, and Bacteroidetes and remained almost stable. However, alpha and beta-diversity analysis revealed a change of the bacterial composition at the final state of the conversion. This change was primarily driven by increasing abundances of the genera Massilia and Lysobacter, both members of the Proteobacteria, after the decay of the leguminous plant residues. Furthermore, increasing abundances of the family Gaiellaceae and its genus Gaiella fostered this change and were related to the decreasing carbon to nitrogen ratio. In short, gentle management strategies could replace the input of mineral fertilizer with the aim to contribute to future sustainable and intensified production even on converted grassland.
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•Strong increase of nitrate-N due to mineralization and biological nitrogen fixation•Bacterial composition on phylum level and bacterial richness remain quite stable.•Beta-diversity analysis indicates changes due to the management practices.•High abundance of Massilia and Lysobacter after incorporation and decay of V. faba•Gentle management strategies can replace the input of mineral fertilizer.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Objectives
The incidence of sexually transmitted hepatitis C virus (HCV) reinfection is on the rise in HIV‐infected men who have sex with men (MSM). Data on natural history of acute hepatitis C and ...possible factors associated with spontaneous clearance are limited. The aim of this study was to analyse the outcome of HCV reinfections in HIV‐positive MSM.
Methods
A retrospective analysis was carried out on patients with more than one sexually acquired HCV infection who were diagnosed at four major German HIV and hepatitis care centres. Reinfection was defined by genotype or phylogenetic clade switch, detectable HCV RNA after a sustained virological response (SVR) or after spontaneous clearance (SC).
Results
In total, 48 HIV‐positive MSM were identified with HCV reinfection, among them 11 with a third episode and one patient with four episodes. At the first episode, 43 and five patients had an SVR and SC, respectively. The second episode was accompanied by a genotype switch in 29 patients (60%). Whereas 30 and nine patients showed an SVR and SC, respectively, eight patients developed chronic hepatitis. Neither HCV genotype switch nor interleukin‐28B genotype was associated with SC. However, SC rates at the second episode were higher for patients with SC at the first episode compared with patients without SC (60 vs. 14%, respectively; P = 0.03). Two patients with SC at the first episode were reinfected with the same genotype.
Conclusions
Multiple reinfections in HIV‐infected MSM do occur, with or without genotype switch, and with prior SC of previous episodes. In this large case series, except for SC at the first episode, no factor was of value in clinical decision‐making for early therapeutic intervention in acute HCV reinfection.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract Background Affective disorders are associated with an increased risk of cardiovascular disease, which, at least partly, appears to be independent of psychopharmacological treatments used to ...manage these disorders. Reduced heart rate variability (SDNN) and a low Omega-3 Index have been shown to be associated with increased risk for death after myocardial infarction. Therefore, we set out to investigate heart rate variability and the Omega-3 Index in euthymic patients with bipolar disorders. Methods We assessed heart rate variability (SDNN) and the Omega-3 Index in 90 euthymic, mostly medicated patients with bipolar disorders (Bipolar-I, Bipolar-II) on stable psychotropic medication, free of significant medical comorbidity and in 62 healthy controls. Heart rate variability was measured from electrocardiography under a standardized 30 minutes resting state condition. Age, sex, BMI, smoking, alcohol consumption and caffeine consumption as potential confounders were also assessed. Results Heart rate variability (SDNN) was significantly lower in patients with bipolar disorders compared to healthy controls (35.4 msec versus 60.7 msec; P < 0.0001), whereas the Omega-3 Index did not differ significantly between the groups (5.2% versus 5.3%). In a linear regression model, only group membership (patients with bipolar disorders versus healthy controls) and age significantly predicted heart rate variability (SDNN). Conclusion Heart rate variability (SDNN) may provide a useful tool to study the impact of interventions aimed at reducing the increased risk of cardiovascular disease in euthymic patients with bipolar disorders. The difference in SDNN between cases and controls cannot be explained by a difference in the Omega-3 Index.
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