Effects of the phosphodiesterase 2 inhibitor BI 474121 on central nervous system cyclic guanosine monophosphate concentrations: Translational studies.

AIMS: Phosphodiesterase 2 (PDE2) regulates intracellular cyclic adenosine monophosphate and guanosine monophosphate (cAMP/cGMP) levels, which contribute to processes crucial for learning and memory. BI 474121, a potent and selective PDE2 inhibitor, is in development for treating cognitive impairment associated with schizophrenia. METHODS: The effects of BI 474121 on cGMP concentrations were first assessed in rat cerebrospinal fluid (CSF) to demonstrate central nervous system (CNS) and functional target engagement. Next, a Phase I study in healthy participants assessed the pharmacokinetics of BI 474121 in CSF vs. plasma, the pharmacodynamics of BI 474121 by measuring cGMP concentrations in the CSF, and the safety of BI 474121. RESULTS: In rats, BI 474121 was associated with a dose-dependent increase (71% at the highest dose tested [3.0 mg kg-1]) in cGMP levels in the CSF relative to vehicle (P < 0.001). In healthy participants, the maximum-measured concentration CSF-to-plasma ratio for BI 474121 exposure was similar following single oral doses of BI 474121 2.5, 10, 20 and 40 mg (dose-adjusted geometric mean: 8.96% overall). BI 474121 2.5-40 mg administration in healthy participants also increased cGMP levels in CSF (maximum exposure-related change from baseline ratio, BI 474121: 1.44-2.20 vs. placebo: 1.26). The most common treatment-emergent adverse event (AE) was mild-to-moderate post-lumbar puncture syndrome, which resolved with standard treatment. No AEs of special interest were observed. CONCLUSIONS: BI 474121 crosses the blood-brain barrier to inhibit PDE2, supporting cGMP as a translational marker to monitor CNS target engagement. These findings promote further clinical development of BI 474121. CLINICALTRIALS: gov number (NCT04672954).

[Diagnosis and Management of Late-Onset Pompe Disease]. / Diagnostik, Therapie und psychosoziale Aspekte bei late-onset Morbus Pompe.

Pompe disease is a lysosomal storage disorder, with onset between the first weeks after birth and adulthood, depending on its phenotype. It can affect multiple organ systems and presents itself with a wide variety of symptoms. Thus, recognizing Pompe disease is difficult. Especially since enzyme replacement therapy for Pompe disease was introduced (in Germany in 2006), early diagnosis by means of enzyme activity determination from dried blood spot analysis and genetic verification has become important for outcome and quality of life. When facing an obscure muscular disorder, it is crucial to consider Pompe disease. This article provides an overview about Pompe disease and focuses on the diagnosis of the late onset type. The most important aspects of interdiciplinary care for patients with Pompe disease are presented. Additionally, it contains a section focusing on psychosocial challenges for children with Pompe disease and their families, which may include mental disorders and social retreat, and gives advice on how to support parents of affected children.

Nintedanib in Progressive Fibrosing Interstitial Lung Diseases.

BACKGROUND: Preclinical data have suggested that nintedanib, an intracellular inhibitor of tyrosine kinases, inhibits processes involved in the progression of lung fibrosis. Although the efficacy of nintedanib has been shown in idiopathic pulmonary fibrosis, its efficacy across a broad range of fibrosing lung diseases is unknown. METHODS: In this double-blind, placebo-controlled, phase 3 trial conducted in 15 countries, we randomly assigned patients with fibrosing lung disease affecting more than 10% of lung volume on high-resolution computed tomography (CT) to receive nintedanib at a dose of 150 mg twice daily or placebo. All the patients met criteria for progression of interstitial lung disease in the past 24 months despite treatment and had a forced vital capacity (FVC) of at least 45% of the predicted value and a diffusing capacity of the lung for carbon monoxide ranging from 30 to less than 80% of the predicted value. Randomization was stratified according to the fibrotic pattern (a pattern of usual interstitial pneumonia [UIP] or other fibrotic patterns) on high-resolution CT. The primary end point was the annual rate of decline in the FVC, as assessed over a 52-week period. The two primary populations for analysis were the overall population and patients with a UIP-like fibrotic pattern. RESULTS: A total of 663 patients were treated. In the overall population, the adjusted rate of decline in the FVC was -80.8 ml per year with nintedanib and -187.8 ml per year with placebo, for a between-group difference of 107.0 ml per year (95% confidence interval [CI], 65.4 to 148.5; P<0.001). In patients with a UIP-like fibrotic pattern, the adjusted rate of decline in the FVC was -82.9 ml per year with nintedanib and -211.1 ml per year with placebo, for a difference of 128.2 ml (95% CI, 70.8 to 185.6; P<0.001). Diarrhea was the most common adverse event, as reported in 66.9% and 23.9% of patients treated with nintedanib and placebo, respectively. Abnormalities on liver-function testing were more common in the nintedanib group than in the placebo group. CONCLUSIONS: In patients with progressive fibrosing interstitial lung diseases, the annual rate of decline in the FVC was significantly lower among patients who received nintedanib than among those who received placebo. Diarrhea was a common adverse event. (Funded by Boehringer Ingelheim; INBUILD ClinicalTrials.gov number, NCT02999178.).

Nintedanib in progressive interstitial lung diseases: data from the whole INBUILD trial.

BACKGROUND: The primary analysis of the INBUILD trial showed that in subjects with progressive fibrosing interstitial lung diseases (ILDs), nintedanib slowed the decline in forced vital capacity (FVC) over 52 weeks. We report the effects of nintedanib on ILD progression over the whole trial. METHODS: Subjects with fibrosing ILDs other than idiopathic pulmonary fibrosis, who had ILD progression within the 24 months before screening despite management deemed appropriate in clinical practice, were randomised to receive nintedanib or placebo. Subjects continued on blinded randomised treatment until all subjects had completed the trial. Over the whole trial, mean±sd exposure to trial medication was 15.6±7.2 and 16.8±5.8 months in the nintedanib and placebo groups, respectively. RESULTS: In the nintedanib (n=332) and placebo (n=331) groups, respectively, the proportions of subjects who had ILD progression (absolute decline in FVC ≥10% predicted) or died were 40.4% and 54.7% in the overall population (hazard ratio (HR) 0.66, 95% CI 0.53-0.83; p=0.0003) and 43.7% and 55.8% among subjects with a usual interstitial pneumonia (UIP)-like fibrotic pattern on high-resolution computed tomography (HRCT) (HR 0.69, 95% CI 0.53-0.91; p=0.009). In the nintedanib and placebo groups, respectively, the proportions who had an acute exacerbation of ILD or died were 13.9% and 19.6% in the overall population (HR 0.67, 95% CI 0.46-0.98; p=0.04) and 15.0% and 22.8% among subjects with a UIP-like fibrotic pattern on HRCT (HR 0.62, 95% CI 0.39-0.97; p=0.03). CONCLUSION: Based on data from the whole INBUILD trial, nintedanib reduced the risk of events indicating ILD progression.

Effects of nintedanib by inclusion criteria for progression of interstitial lung disease.

BACKGROUND: The INBUILD trial investigated nintedanib versus placebo in patients with progressive fibrosing interstitial lung diseases (ILDs). We investigated the decline in forced vital capacity (FVC) in subgroups based on the inclusion criteria for ILD progression. METHODS: Subjects had a fibrosing ILD other than idiopathic pulmonary fibrosis and met the following criteria for ILD progression within the 24 months before screening despite management deemed appropriate in clinical practice: Group A, relative decline in FVC ≥10% predicted; Group B, relative decline in FVC ≥5-<10% predicted with worsened respiratory symptoms and/or increased extent of fibrosis on high-resolution computed tomography (HRCT); Group C, worsened respiratory symptoms and increased extent of fibrosis on HRCT only. RESULTS: In the placebo group, the rates of FVC decline over 52 weeks in Groups A, B and C, respectively, were -241.9, -133.1 and -115.3 mL per year in the overall population (p=0.0002 for subgroup-by-time interaction) and -288.9, -156.2 and -100.1 mL per year among subjects with a usual interstitial pneumonia (UIP)-like fibrotic pattern on HRCT (p=0.0005 for subgroup-by-time interaction). Nintedanib had a greater absolute effect on reducing the rate of FVC decline in Group A than in Group B or C. However, the relative effect of nintedanib versus placebo was consistent across the subgroups (p>0.05 for heterogeneity). CONCLUSIONS: The inclusion criteria used in the INBUILD trial, based on FVC decline or worsening of symptoms and extent of fibrosis on HRCT, were effective at identifying patients with progressive fibrosing ILDs. Nintedanib reduced the rate of decline in FVC across the subgroups based on the inclusion criteria related to ILD progression.

Predictors of mortality in subjects with progressive fibrosing interstitial lung diseases.

BACKGROUND AND OBJECTIVE: Demographic and clinical variables, measured at baseline or over time, have been associated with mortality in subjects with progressive fibrosing interstitial lung diseases (ILDs). We used data from the INPULSIS trials in subjects with idiopathic pulmonary fibrosis (IPF) and the INBUILD trial in subjects with other progressive fibrosing ILDs to assess relationships between demographic/clinical variables and mortality. METHODS: The relationships between baseline variables and time-varying covariates and time to death over 52 weeks were analysed using pooled data from the INPULSIS trials and, separately, the INBUILD trial using a Cox proportional hazards model. RESULTS: Over 52 weeks, 68/1061 (6.4%) and 33/663 (5.0%) subjects died in the INPULSIS and INBUILD trials, respectively. In the INPULSIS trials, a relative decline in forced vital capacity (FVC) >10% predicted within 12 months (hazard ratio [HR] 3.77) and age (HR 1.03 per 1-year increase) were associated with increased risk of mortality, while baseline FVC % predicted (HR 0.97 per 1-unit increase) and diffusing capacity of the lungs for carbon monoxide (DLCO) % predicted (HR 0.77 per 1-unit increase) were associated with lower risk. In the INBUILD trial, a relative decline in FVC >10% predicted within 12 months (HR 2.60) and a usual interstitial pneumonia-like fibrotic pattern on HRCT (HR 2.98) were associated with increased risk of mortality, while baseline DLCO % predicted (HR 0.95 per 1-unit increase) was associated with lower risk. CONCLUSION: These data support similarity in the course of lung injury between IPF and other progressive fibrosing ILDs and the value of FVC decline as a predictor of mortality.

Two first-in-human studies of xentuzumab, a humanised insulin-like growth factor (IGF)-neutralising antibody, in patients with advanced solid tumours.

BACKGROUND: Xentuzumab, an insulin-like growth factor (IGF)-1/IGF-2-neutralising antibody, binds IGF-1 and IGF-2, inhibiting their growth-promoting signalling. Two first-in-human trials assessed the maximum-tolerated/relevant biological dose (MTD/RBD), safety, pharmacokinetics, pharmacodynamics, and activity of xentuzumab in advanced/metastatic solid cancers. METHODS: These phase 1, open-label trials comprised dose-finding (part I; 3 + 3 design) and expansion cohorts (part II; selected tumours; RBD [weekly dosing]). Primary endpoints were MTD/RBD. RESULTS: Study 1280.1 involved 61 patients (part I: xentuzumab 10-1800 mg weekly, n = 48; part II: 1000 mg weekly, n = 13); study 1280.2, 64 patients (part I: 10-3600 mg three-weekly, n = 33; part II: 1000 mg weekly, n = 31). One dose-limiting toxicity occurred; the MTD was not reached for either schedule. Adverse events were generally grade 1/2, mostly gastrointestinal. Xentuzumab showed dose-proportional pharmacokinetics. Total plasma IGF-1 increased dose dependently, plateauing at ~1000 mg/week; at ≥450 mg/week, IGF bioactivity was almost undetectable. Two partial responses occurred (poorly differentiated nasopharyngeal carcinoma and peripheral primitive neuroectodermal tumour). Integration of biomarker and response data by Bayesian Logistic Regression Modeling (BLRM) confirmed the RBD. CONCLUSIONS: Xentuzumab was well tolerated; MTD was not reached. RBD was 1000 mg weekly, confirmed by BLRM. Xentuzumab showed preliminary anti-tumour activity. CLINICAL TRIAL REGISTRATION: NCT01403974; NCT01317420.

The natural history of progressive fibrosing interstitial lung diseases.

We used data from the INBUILD and INPULSIS trials to investigate the natural history of progressive fibrosing interstitial lung diseases (ILDs).Subjects in the two INPULSIS trials had a clinical diagnosis of idiopathic pulmonary fibrosis (IPF) while subjects in the INBUILD trial had a progressive fibrosing ILD other than IPF and met protocol-defined criteria for ILD progression despite management. Using data from the placebo groups, we compared the rate of decline in forced vital capacity (FVC) (mL·year-1) and mortality over 52 weeks in the INBUILD trial with pooled data from the INPULSIS trials.The adjusted mean annual rate of decline in FVC in the INBUILD trial (n=331) was similar to that observed in the INPULSIS trials (n=423) (-192.9 mL·year-1 and -221.0 mL·year-1, respectively; nominal p-value=0.19). The proportion of subjects who had a relative decline in FVC >10% predicted at Week 52 was 48.9% in the INBUILD trial and 48.7% in the INPULSIS trials, and the proportion who died over 52 weeks was 5.1% in the INBUILD trial and 7.8% in the INPULSIS trials. A relative decline in FVC >10% predicted was associated with an increased risk of death in the INBUILD trial (hazard ratio 3.64) and the INPULSIS trials (hazard ratio 3.95).These findings indicate that patients with fibrosing ILDs other than IPF, who are progressing despite management, have a subsequent clinical course similar to patients with untreated IPF, with a high risk of further ILD progression and early mortality.

Afatinib plus vinorelbine versus trastuzumab plus vinorelbine in patients with HER2-overexpressing metastatic breast cancer who had progressed on one previous trastuzumab treatment (LUX-Breast 1): an open-label, randomised, phase 3 trial.

BACKGROUND: Trastuzumab resistance is a key therapeutic challenge in metastatic breast cancer. We postulated that broader inhibition of ErbB receptors with afatinib would improve clinical outcomes compared with HER2 inhibition alone in patients who had progressed on previous trastuzumab treatment. LUX-Breast 1 compared afatinib plus vinorelbine with trastuzumab plus vinorelbine for such patients with HER2-positive metastatic breast cancer. METHODS: We did this open-label trial at 350 hospitals in 41 countries worldwide. We enrolled female patients with HER2-overexpressing metastatic breast cancer who had progressed on or following adjuvant trastuzumab or first-line treatment of metastatic disease with trastuzumab. Participants were randomly assigned (2:1) to receive oral afatinib (40 mg/day) plus intravenous vinorelbine (25 mg/m(2) per week) or intravenous trastuzumab (2 mg/kg per week after 4 mg/kg loading dose) plus vinorelbine. Randomisation was done centrally and stratified by previous trastuzumab treatment (adjuvant vs first-line treatment), hormone receptor status (oestrogen receptor and progesterone receptor positive vs others), and region. The primary endpoint was progression-free survival, assessed in the intention-to-treat population. This trial is closed to enrolment and is registered with ClinicalTrials.gov, NCT01125566. FINDINGS: Between Aug 26, 2010, and April 26, 2013, we enrolled 508 patients: 339 assigned to the afatinib group and 169 assigned to the trastuzumab group. Recruitment was stopped on April 26, 2013, after a benefit-risk assessment by the independent data monitoring committee was unfavourable for the afatinib group. Patients on afatinib plus vinorelbine had to switch to trastuzumab plus vinorelbine, afatinib monotherapy, vinorelbine monotherapy, or receive treatment outside of the trial. Median follow-up was 9·3 months (IQR 3·7-16·0). Median progression-free survival was 5·5 months (95% CI 5·4-5·6) in the afatinib group and 5·6 months (5·3-7·3) in the trastuzumab group (hazard ratio 1·10 95% CI 0·86-1·41; p=0·43). The most common drug-related adverse events of grade 3 or higher were neutropenia (190 [56%] of 337 patients in the afatinib group vs 102 [60%] of 169 patients in the trastuzumab group), leucopenia (64 [19%] vs 34 [20%]), and diarrhoea (60 [18%] vs none). INTERPRETATION: Trastuzumab-based therapy remains the treatment of choice for patients with HER2-positive metastatic breast cancer who had progressed on trastuzumab. FUNDING: Boehringer Ingelheim.

A phase 1 dose escalation study of BI 831266, an inhibitor of Aurora kinase B, in patients with advanced solid tumors.

Purpose BI 831266 is a potent, selective, low-molecular-weight inhibitor of Aurora kinase B. This trial aimed to determine the maximum tolerated dose (MTD) of BI 831266 in patients with advanced solid tumors (NCT00756223; EudraCT 2008-001631-36; 1257.1). Methods BI 831266 (4-130 mg) was administered over 24 h on days 1 and 15 of a 4-week schedule. A modified 3 + 3 dose-escalation design was utilized to evaluate the MTD. Safety, pharmacokinetics, pharmacodynamics, objective response rate, progression-free survival (PFS) and exploratory biomarkers were secondary endpoints. Results Twenty-five patients received BI 831266. The most frequent tumor type was colorectal cancer (48%). One patient (130 mg) experienced a dose-limiting toxicity of grade 3 febrile neutropenia. The trial was prematurely terminated (sponsor decision) without further dose-escalation. The most frequent treatment-related adverse events (AEs) were fatigue (20%), neutropenia, alopecia (16% each), anemia, dry skin, and nausea (12% each). Treatment-related grade ≥3 AEs were neutropenia (12%), anemia (8%), and febrile neutropenia (4%); 15 patients experienced serious AEs. High variability in the pharmacokinetic profiles precluded definitive pharmacokinetic conclusions. Exploratory biomarker determination revealed consistency with the mode of action as an Aurora kinase B inhibitor. One patient (4%; 32 mg) with cervical cancer demonstrated a confirmed partial response (duration 141 days, PFS 414 days). Four patients had stable disease. Conclusion The MTD of BI 831266 was not reached because of early trial termination. BI 831266 demonstrated a generally manageable safety profile and signs of antitumor activity in some patients' solid tumors.

Changes in soil microbial biomass and residual indices as ecological indicators of land use change in temperate permanent grassland.

The relationship between microbial biomass, residues and their contribution to microbial turnover is important to understand ecosystem C storage. The effects of permanent grassland (100 % ryegrass--PG), conversion to modified grassland (mixture of grass and clover--MG) or maize monoculture (MM) on the dynamics of soil organic C (SOC), microbial biomass, fungal ergosterol and microbial residues (bacterial muramic acid and fungal glucosamine) were investigated. Cattle slurry was applied to quantify the effects of fertilisation on microbial residues and functional diversity of microbial community across land use types. Slurry application significantly increased the stocks of microbial biomass C and S and especially led to a shift in microbial residues towards bacterial tissue. The MM treatment decreased the stocks of SOC, microbial biomass C, N and S and microbial residues compared with the PG and MG treatments at 0-40 cm depth. The MM treatment led to a greater accumulation of saprotrophic fungi, as indicated by the higher ergosterol-to-microbial biomass C ratio and lower microbial biomass C/S ratio compared with the grassland treatments. The absence of a white clover population in the PG treatment caused a greater accumulation of fungal residues (presumably arbuscular mycorrhizal fungi (AMF), which do not contain ergosterol but glucosamine), as indicated by the significantly higher fungal C-to-bacterial C ratio and lower ergosterol-to-microbial biomass C ratio compared with the MG treatment. In addition to these microbial biomass and residual indices, the community level physiological profiles (CLPP) demonstrated distinct differences between the PG and MG treatments, suggesting the potential of these measurements to act as an integrative indicator of soil functioning.

Perspectives of clinical medical directors in child and adolescent psychiatry: diagnostic and treatment needs of migrant families.

Germany is one of many nations characterized by an increasing number of children originating from families with a migration background. Medical treatment modalities will be required to adjust for diversity of social and cultural background. Initiated by the Federal Society of Child and Adolescent Psychiatry (BKJPP), representing mainly those psychiatrists working in private practice, and by the Federal Working Commission of Medical Directors employed in Child and Adolescent Psychiatric Clinics (BAG), a questionnaire was constructed to identify mental health professionals' (psychiatrists') evaluation of the needs and quality of diagnosis and treatment for migrant families. The current study focused on medical directors and deputy chief physicians in clinics for child and adolescent psychiatry. Preliminary results of this survey - implementing descriptive statistics as well as univariate and multivariate statistical analyses - permitted an assessment of the current state of identification and treatment of migrant offspring attending child and adolescent psychiatric practices in Germany. Recommendations and concrete steps are offered, which aim to promote "cultural opening", and assist in health and social policy makers' decisions for improved mental health care.

Galactosamine and mannosamine are integral parts of bacterial and fungal extracellular polymeric substances.

Extracellular polymeric substances (EPS) are produced by microorganisms and interact to form a complex matrix called biofilm. In soils, EPS are important contributors to the microbial necromass and, thus, to soil organic carbon (SOC). Amino sugars (AS) are used as indicators for microbial necromass in soil, although the origin of galactosamine and mannosamine is largely unknown. However, indications exist that they are part of EPS. In this study, two bacteria and two fungi were grown in starch medium either with or without a quartz matrix to induce EPS production. Each culture was separated in two fractions: one that directly underwent AS extraction (containing AS from both biomass and EPS), and another that first had EPS extracted, followed then by AS determination (exclusively containing AS from EPS). We did not observe a general effect of the quartz matrix neither of microbial type on AS production. The quantified amounts of galactosamine and mannosamine in the EPS fraction represented on average 100% of the total amounts of these two AS quantified in cell cultures, revealing they are integral parts of the biofilm. In contrast, muramic acid and glucosamine were also quantified in the EPS, but with much lower contribution rates to total AS production, of 18% and 33%, respectively, indicating they are not necessarily part of EPS. Our results allow a meaningful ecological interpretation of mannosamine and galactosamine data in the future as indicators of microbial EPS, and also attract interest of future studies to investigate the role of EPS to SOC and its dynamics.

Dose-dependent reactions of Aporrectodea caliginosa to perfluorooctanoic acid and perfluorooctanesulfonic acid in soil.

As a consequence of their widespread use, e.g. as protective coatings for fabrics, and their resistance to thermal and biological breakdown, perfluorinated compounds are increasingly found in the environment, but little is known about their ecotoxicological properties. A 40-day microcosm experiment was carried out to examine the effects of perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) on the endogeic geophagus earthworm Aporrectodea caliginosa, its survival and feeding on soil organic C and microbial biomass C. Three levels of concentration (1, 100, and 500 mg kg(-1)) were chosen. The lowest represented the maximum found in sediments and soils and the other two are extreme concentrations that might occur in pollution hotspots and that have been shown to poison organisms. Earthworms promoted the production of CO2 and decreased microbial biomass C in soil, regardless of the presence of PFOA or PFOS. Both compounds significantly decreased the surviving numbers and dry weight of earthworms at concentrations of 100 mg kg(-1). No earthworms survived at PFOA and PFOS concentrations of 500 mg kg(-1). At concentrations of 1 mg kg(-1), no negative effects were observed. The δ(13)C values of A. caliginosa did not differ between treatments. In contrast, the δ(15)N values were significantly increased after adding 1 mg kg(-1) of PFOA, reflecting elevated portions of soil-derived N in the earthworm tissue. In contrast, these portions of soil-derived N were lower in the earthworms after addition of 100 mg kg(-1) of PFOA and PFOS. In conclusion, extreme concentrations of PFOA and PFOS negatively affected endogeic A. caliginosa, whereas a concentration of 1 mg kg(-1) of PFOA and PFOS was related to an increased uptake of soil N by the earthworms.

Health and educational performance among young migrants.

This study is a part replication of an earlier study by on health efficacy, educational attainment and well-being among 30 nations. It includes, however, data from these nations, as well as the latest Pisa results and update socioeconomic data and sociological variables which include divorce rate, number of persons/household, employment rates, and measures of physical and mental health (including new scales of well-being, e.g., mental health index, life satisfaction, suicide rates). More importantly, it includes measures of migrant rates among children and adults in each country, the focus of attention of this article. New material on health and educational expenditure are provided.

The Effects of Conservation Tillage on Chemical and Microbial Soil Parameters at Four Sites across Europe.

Conservation tillage is often discussed as an effective tool to improve the soil quality in agriculture. Four sites across Europe (in Germany, Romania, Spain, and Sweden) were investigated as case studies for country-specific reductions in tillage intensity. Conventional tillage (CT) by mouldboard ploughing was compared with shallow and deep non-inversion minimum tillage (MT) and/or no-tillage (NT). In Sweden, NT and MT had positive effects on the concentrations of soil organic carbon (SOC), total nitrogen (N), and microbial biomass carbon (MBC) in the upper 20 cm compared with CT. At the German site, MT increased SOC, N, and MBC concentrations in the top 10 cm. In contrast, CT increased MBC contents and bulk density between 20 and 30 cm soil depth. At the Romanian site, soil parameters showed no differences between inverse tillage (CT) and non-inverse tillage (MT), both with a working depth of 25 to 30 cm. At the Spanish site, the use of NT significantly increased the concentrations as well as the stocks of C, N, and MBC compared to CT. In conclusion, reduced tillage improved soil microbial properties in most cases. However, the effectiveness of reduced tillage appears to be highly dependent on site conditions such as pH, soil texture, and climatic conditions.

Soil microbial properties of subalpine steppe soils at different grazing intensities in the Chinese Altai Mountains.

Long-term provision of ecosystem services by grasslands is threatened by increasing stocking densities. The functions of grassland ecosystems depend on a mutual relationship between aboveground and belowground biota. While the effects of increasing stocking density on plant biomass are well studied, little is known about its impact on soil microbial properties. To fill this knowledge gap a grazing experiment was conducted on a summer pasture in the Chinese Altai Mountains during the summers of 2014 and 2015 using a randomized block design with stocking densities of 0, 8, 16, and 24 sheep ha-1 replicated four times. After two summer grazing periods (each 56 days), topsoil samples (1-7 cm) were taken in September 2015 and analyzed for major physical, chemical, and microbial soil properties. Except for the metabolic quotient (qCO2; p < 0.05), the examined soil properties remained unaffected by the increasing stocking densities, likely due to high spatial variability. The qCO2 declined from 13.5 mg CO2-C g-1 microbial biomass C d-1 at zero grazing to 12.2 mg CO2-C g-1 microbial biomass C d-1 at a stocking density of 24 sheep ha-1. Low values of qCO2 indicate an aged and dormant microbial community that diverts less soil organic carbon (SOC) to catabolic processes within their cells, characteristic for C limiting conditions. The aboveground biomass affected by grazing intensity correlated positively with SOC (rs = 0.60, p = 0.015) and ergosterol (rs = 0.76, p = 0.001) pointing indirectly to the effect of stocking density. Additionally to the relatively high values of qCO2, highest values of SOC (39.2 mg g-1 soil), ergosterol (6.01 µg g-1 soil), and basal respiration (10.7 µg g-1 soil d-1) were observed at a stocking density of 8 sheep ha-1 indicating that a low grazing intensity is recommendable to avoid soil degradation.

Functions of elements in soil microorganisms.

The soil microbial community fulfils various functions, such as nutrient cycling and carbon (C) sequestration, therefore contributing to maintenance of soil fertility and mitigation of global warming. In this context, a major focus of research has been on C, nitrogen (N) and phosphorus (P) cycling. However, from aquatic and other environments, it is well known that other elements beyond C, N, and P are essential for microbial functioning. Nonetheless, for soil microorganisms this knowledge has not yet been synthesised. To gain a better mechanistic understanding of microbial processes in soil systems, we aimed at summarising the current knowledge on the function of a range of essential or beneficial elements, which may affect the efficiency of microbial processes in soil. This knowledge is discussed in the context of microbial driven nutrient and C cycling. Our findings may support future investigations and data evaluation, where other elements than C, N, and P affect microbial processes.

Evidence of considerable C and N transfer from peas to cereals via direct root contact but not via mycorrhiza.

Intercropping of legumes and cereals is an important management method for improving yield stability, especially in organic farming systems. However, knowledge is restricted on the relevance of different nutrient transfer pathways. The objective of the study was to quantify nitrogen (N) and carbon (C) transfer from peas to triticale by (1) direct root contact (= R), (2) arbuscular mycorrhizal fungi (AMF; = A), and (3) diffusion (= D). Pea (Pisum sativum cv. Frisson and P2) and triticale (Triticum × Secale cv. Benetto) plants as intercrop were grown for 105 days. Treatment ADR enabled all transfer paths between the two crops. Treatment AD with root exclusion enabled AMF and diffusion transfer between peas and triticale. Treatment A with a diffusion gap barrier only allowed AMF transfer. Pea plants were labelled every 14 days with a 13C glucose and 15N urea solution, using the cotton wick technique. Direct root contact resulted in the highest pea rhizodeposition and thus the largest absolute amounts of N and C transfer to triticale. Root exclusion generally changed composition of rhizodeposits from fine root residues towards root exudates. Pea plant-N consisted of 17% N derived from rhizodeposition (NdfR) in treatment ADR but only 8% in the treatments AD and A, independently of pea variety, whereas pea plant-C consisted of 13% C derived from rhizodeposition (CdfR), without pea variety and transfer path treatment effects. Averaging all transfer path treatments, 6.7% of NdfR and 2.7% of CdfR was transferred from Frisson and P2 to triticale plants. Approximately 90% of this NdfR was transferred by direct root contact from Frisson to triticale and only 10% by AMF, whereas only 55% of CdfR was transferred to triticale by direct root contact, 40% by AMF and 5% by diffusion. Similar percentages were transferred from mutant P2 to triticale. Root exclusion generally changed RD composition from fine root residues towards root exudates.