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PURPOSE Interferon alfa-2b (IFN alpha-2b) exhibits antitumor activity in metastatic melanoma and on this basis has been evaluated as an adjuvant therapy following surgery for deep primary (T4) or regionally metastatic (N1) melanoma. METHODS A randomized controlled study of IFN alpha-2b (Schering-Plough, Kenilworth, NJ) administered at maximum-tolerated doses of 20 MU/m2/d intravenously (i.v.) for 1 month and 10 MU/m2 three times per week subcutaneously (SC) for 48 weeks versus observation, was conducted by the Eastern Cooperative Oncology Group (ECOG) in 287 patients. RESULTS A significant prolongation of relapse-free survival (P = .0023, one-sided) and prolongation of overall survival (P = .0237, one-sided) was observed with IFN alpha-2b therapy in this trial, which is now mature with a median follow-up time of 6.9 years. The impact of treatment on relapse rate is most pronounced early during the treatment interval. The overall benefit of treatment in this trial was analyzed stratified by tumor burden and the presence or absence of microscopic nonpalpable and palpable regional lymph node metastasis. The benefit of therapy with IFN alpha-2b was greatest among node-positive strata. Toxicity of IFN alpha-2b required dose modification in the majority of patients, but treatment at > or = 80% of the scheduled dose was feasible in the majority of patients through the IV phase of treatment, and for more than 3 months of SC maintenance therapy. Discontinuation of treatment due to toxicity was infrequent after the fourth month of therapy. CONCLUSION IFN alpha-2b prolongs the relapse-free interval and overall survival of high-risk resected melanoma patients. The increment in median disease-free survival (from 1 to 1.7 years) and overall survival (from 2.8 to 3.8 years) that results from this therapy is associated with a 42% improvement in the fraction of patients who are continuously disease-free after treatment with IFN (from 26% to 37%) in comparison to observation. IFN alpha-2b is the first agent to show a significant benefit in relapse-free and overall survival of high-risk melanoma patients in a randomized controlled trial.

BACKGROUND: Reflective practice is associated with improved accuracy of medical diagnosis and superior performance in complex situations. Systematic observation of trainees’ reflective capacities constitutes a basis for an effective support of reflective practice within the training paradigm. We set out to examine the reflective capacity among anesthesiology trainees in a tertiary referral hospital. METHODS: We invited 61 anesthesiology trainees in Cork University Hospitals, Ireland, to participate. Each trainee was invited to respond to 2 investigator-written vignettes prepared by the investigators and suitable for evaluation using the Reflection Evaluation for Learners’ Enhanced Competencies Tool (REFLECT) and to produce and then respond to a written vignette based on their own experience. All responses were assessed by 2 independent assessors who had undergone training in the application of the REFLECT rubric, which gives quantifiable scores. Interrater reliability was assessed by weighted kappa coefficient. Association between years of training in medicine and level of reflective capacity was examined using correlation and multiple regression analyses, controlling for age. RESULTS: Twenty-nine trainees agreed to participate, the overall REFLECT Level was 2.16 (SD 0.7), corresponding to “thoughtful action,” indicating low to moderate reflective ability. Cronbach’s alpha for the 5 items of the REFLECT scale was excellent (r = 0.92). Weighted kappa was very satisfactory (k = 0.81). A strong association was demonstrated between years in medicine and scores on REFLECT, controlling for age of participant (F = −2.57, Beta coefficient = −0.30). Respondents with less experience had greater mean REFLECT scores than respondents with more experience (F = 5.5, P = .02; post hoc mean difference = 0.7, P = .03 for ≤32 months vs ≥99 months). There was a significant effect for gender (t = −4.3, P = .001), with women’s responses receiving greater REFLECT scores than men’s responses (mean difference = 0.67, P = .001). CONCLUSIONS: Overall, participants demonstrated low to moderate reflective capacity, as assessed by the REFLECT rubric. Reflective capacity of the anesthesiology trainees appears to decrease as years of medical training progress. However, our respondents were not sampled over time to fully support this conclusion. Further research is needed on the psychometric properties of the REFLECT rubric and the generalizability of our findings.

Soils, the thin skin of the earth, a living body, are the basis of all highly developed life and have ensured human existence and culture since millennia. Their functions and ecosystem services are crucial for the survival of humanity. Increasing pressure on soils through overuse and mismanagement has exceeded their capacity to perform, which is considered as soil degradation. To meet the mission of the Sustainable Development Goals of the United Nations, soil degradation must be stopped and reversed. We reviewed framework conditions of soil degradation, scientific concepts of research and status and trends of their operationalization. Soil performance and degradation processes must be understood, monitored, mitigated and combated in the context of different categories and scales such as ecosystems, land and landscapes. Approaches to the assessment and monitoring of soil dynamics, degradation and desertification show inconsistencies and knowledge gaps at several levels. Concepts of soil health and ecosystem services of soil should be backed by “hard data” based on field and landscape indicators and measurements. Participatory approaches to mediate conflicting demands of stakeholders are crucial for a broad understanding of soil and its long-term sustainable use. This requires an advanced field diagnostic system of soil performance based on reliable on-site measurement technology in combination with expert-based knowledge and assessment methodologies. Strengthening field soil science is essential for progress in reducing and reversing soil degradation.

Physical soil degradation is a deterioration of the soil’s structure diminishing its functions and ecosystem services. It is mainly initiated and manifested by physical forces and processes, such as energy impacts of water, wind and mechanical pressure on soils, and it is accelerated by various kinds of anthropogenic pressure. This is a threat to meeting visions of the Sustainable Development Goals of the United Nations. We review the current state of some types of physical soil degradation, such as erosion by water, wind and tillage, soil compaction and soil sealing/land take. Despite some knowledge in research of degradation processes, gaps in knowledge and need for action exist at several levels. There is a need to understand the event-wise, stochastic character of erosion and compaction processes and the complex interaction of mechanical disturbances of soil structure with soil hydrological and biochemical processes. The implications of these processes for soil health and ecosystem functioning must be better quantified, yielding indicators, baseline values and thresholds. Progress is needed to develop simulation models of soil erosion and compaction towards complex modular models that can figure and forecast ecosystem processes. There is a demand to construct manageable decision support systems, which can help to plan and conduct zero-soil degradation projects at a landscape level. Cross-comparisons of models and strengthening the databases in terms of field laboratories and long-term experiments are essential to prevent and monitor soil degradation at different scales.

Hoffman syndrome is a syndromic, inborn error of immunity due to autosomal-dominant mutations in TOP2B, an essential gene required to alleviate topological stress during DNA replication and gene transcription. Although mutations identified in patients lead to a block in B-cell development and the absence of circulating B cells, an effect on natural killer (NK) cells was not previously examined.We sought to determine whether disease-associated mutations in TOP2B impact NK-cell development and function.Using a knockin murine model and patient-derived induced pluripotent stem cells (iPSCs), we investigated NK-cell development in mouse bone marrow and spleen, and performed immunophenotyping by flow cytometry, gene expression, and functional assessment of cytotoxic activity in murine NK cells, and human IPSC-derived NK cells.Mature NK cells were reduced in the periphery of TOP2B knockin mice consistent with patient reports, with reduced cytotoxicity toward target cell lines. IPSCs were successfully derived from patients with Hoffman syndrome, but under optimal conditions showed reduced cytotoxicity compared with iPSC-derived NK cells from healthy controls.Hoffman syndrome-associated mutations in TOP2B impact NK-cell development and function in murine and human models.

BackgroundThe pathogenesis of Spondyloarthritis (SpA) remains unknown but its strong association with some alleles of HLA-B*27 is peculiar. The arthritogenic antigen hypothesis assumes the existence of specific peptides presented by risk-conferring HLA-B*27 alleles to antigen-specific CD8+ T cells, which then initiate or sustain autoimmune reactions. Several studies analyzing T cell receptor (TCR) repertoire found preferred Variable TCR chains and motifs in the hypervariable complementary determining region (CDR) 3, but analyzed only TCR β-chains in bulk analyses1,2.ObjectivesTo analyze full sequence information of TCR including matching α- and β-chains from single CD8+ T cells and characterize the transcriptomes of expanded and non-expanded clonotypes in synovial fluid (SF) of SpA patients.MethodsWe included 17 patients with active gonarthritis: 10 patients with HLA-B27 positive (B27pos) SpA, 4 with HLA-B27 negative (B27neg) SpA and 3 rheumatoid arthritis (RA) patients. Antigen-experienced CD8+ T cells were sorted out of SF by flow cytometry. Single cell sequencing was performed for all patients to analyze matching TCR α- and β-chains. For 7 patients (3 B27pos SpA, 2 B27neg SpA, 2 RA), additionally whole transcriptome analyses were performed.ResultsWe found strong biases when analyzing α and β chains of TCR Variable regions and CDR1 and CDR2 sequences (Figure 1 a,b): AV21, AV12-2, and AV17 were highly enriched in B27pos SpA as compared to B27neg subjects. Amongst the highest expressed clones, we could confirm enrichment for previously described TRBV genes as BV19, BV5-1 and BV6-2. We examined TCR α/β combinations and focused on those detected in at least three different B27pos SpA but not in any of the B27neg patients (Figure 1 c-f). The combinations TRBV19/TRAV21 and TRBV6-2/TRAV21 were most likely specific for B27pos SpA and might reflect interaction of these TCR chains with HLA-B*27. Sequences of CDR3 loops, which predominantly interact with HLA-bound antigenic peptides, revealed striking common structural motifs in α- and β-chains. Focusing on the most prominent TRAV21 chains pairing with TRBV19, 5-1 and 6-2 chains, revealed identical sequences in different patients and striking common structural motifs in α- and β-CDR3 sequences in other patients. Such marked similarities in the antigen-recognition loops of the β-chains associated with TRAV21 suggest common or highly similar antigens. Gene expression levels provided evidence that expanded cell populations had tissue resident memory (TRM) phenotypes (elevated expression of activation, migration and tissue retention markers, downregulated genes characteristic for T cell egress), while this phenotype was not very pronounced in non-expanded cells. Furthermore, markers for T cell exhaustion and apoptosis were elevated in expanded cells of B27pos SpA patients.Figure 1.Distinct TCRαβ V chain usage in expanded clones from HLA-B27 positive SpA patients. A,B Mean number of all productive TRAV (A) and TRBV (B) genes used in expanded, antigen-experienced CD8 T cell clones (>1% of all cells) from SF of 10 B27pos SpA, 4 B27neg SpA and 3 B27neg RA patients. C-F TRAV chains paired with TRBV19 (C), TRBV5-1 (D), TRBV6-2 (E), or TRBV chains paired with TRAV21 (F) with corresponding TRAJ spanning partners in expanded cells (frequency ≥2) from all 10 B27pos SpA. Number of chains are 1250 (C), 886 (D), 1220 (E), and 4006 (F).ConclusionAnalysis of single antigen experienced CD8+ T cells from SF of B27pos SpA patients revealed significant clonal expansions and common motifs in the CDR loops. Two of the four CDR1 and CDR2 loops were highly homologous suggesting that these loops interact with α-helices of HLA-B*27. Common motifs in CDR3 loops of expanded clonotypes suggest recognition of a limited set of antigenic peptides presented by HLA-B*27. Many of the expanded clonotypes showed a TRM phenotype, were exhausted and on the way to become apoptotic, which suggests that these clones had sustained contact to specific antigens.References[1]Komech, et al. Rheumatology 2018[2]Hanson, et al. A&R 2020AcknowledgementsWe thank all patients included in this study for their participation. This work was funded by the German Research Foundation (DFG) through grants DO 420/4 to KDo, PO 2124/2-1 to DP, and SyNergy (EXC 2145 SyNergy – ID 390857198) to KDo. Judith Rademacher and Katharina Deschler contributed equally. JR is participant in the BIH-Charité Clinician Scientist Program funded by the Charité –Universitätsmedizin Berlin and the Berlin Institute of Health. The authors would like to thank Martina Seipel for excellent technical assistance, Sabrina Sron for patient recruitment and study coordination, and Hildrun Haibel, Mikhail Protopopov, Fabian Proft, Valeria Rios Rodriguez and Laura Spiller for recruiting patients for this study.Disclosure of InterestsNone declared

Sustainable intensification (SI) is a concept for increasing agricultural production under sustainable conditions to meet the needs of the worldwide growing population. We reviewed the status and trends of SI on the basis of latest scientific publications. Some progress was found in evolving the concept of SI for meeting the Sustainable Development Goals of the United Nations. However, gaps in knowledge and quantitative data are largely missing. To achieve progress in understanding and evolving SI, knowledge about soils is of paramount importance. Soil data are suitable indicators for sustainable land-use practices. We used data of soil resilience and productivity for assessing land potentials for SI. Six intrinsic land and soil characteristics (organic C content, clay + silt, pH, CEC, soil depth and slope) were selected as indictors for defining the resilience and performance of land in Europe. These six indicators comprise the main biochemical and physical soil properties. To analyze the potential of SI in EU-25, the above described approach was based on LUCAS 2009 topsoil data, using the dataset of the arable land in the Corine Land Use Cover 2006 as well as to the European Soil Database (ESDB). The results show that due to a low natural resilience and productivity of soils, almost half (44%) of the investigated arable land cannot be recommended for SI. More than 3% of this area should be de-intensified in order to reduce environmental harm. 16% of the arable land can be recommended for SI with restrictions, whereas 40% of arable land has the potential for SI without impacting the delivery of goods and services provided by soils. As Europe is a region of suitable bio-climatic and societal conditions for sustainable land management, serious limitations for SI must be expected in other parts of the globe. Interdisciplinary studies should clarify this problem.

Agricultural landscapes (rural landscapes, agrolandscapes) are territories shaped by agricultural production. They have enabled the development of human civilizations and are a cultural achievement. Peasants, farmers and agricultural enterprises feed society. They have created agricultural landscapes for their business and habitats for their life. To understand transformation processes in agricultural landscapes, we analyse the history of agriculture with a special focus on Europe and Eurasia. Current agricultural landscapes in a crowded, globalized world are multifunctional, highly complex systems. They not only serve to produce food commodities and energy for the increasing and expanding urban population but also provide diverse ecosystem services and need to cater for the demands of the rural population. Current agriculture is highly productive in wealthy countries, but due to high inputs it is also responsible for environmental problems such as water pollution and loss of biodiversity. Industrial-style agriculture in large fields has resulted in increased productivity but simplified the structure of landscapes and eliminated elements of nature and rural culture. Major problems that urgently need to be addressed include trends towards disrupting natural cycles in agricultural production, soil and water degradation, ageing populations in villages and the breakdown of rural infrastructure. Agricultural landscape research provides analyses to understand these processes and helps elaborate sustainable scientific, technical and cultural solutions.

Fil: Mueller, Lothar. Leibniz Centre for Agricultural Landscape Research. Alemania. Fil: Eulenstein, Frank. Leibniz Centre for Agricultural Landscape Research. Alemania. Fil: Mirschel, Wilfried. Leibniz Centre for Agricultural Landscape Research. Alemania. Fil: Schindler, Uwe. Kuban State Agrarian University. Rusia. Fil: Sychev, Viktor G. Pryanishnikov-Institute for Agrochemistry. Rusia. Fil: Rukhovich, Olga V. Pryanishnikov-Institute for Agrochemistry. Rusia. Fil: Sheudzhen, Askhad K. Kuban State Agrarian University. Rusia. Fil: Romanenkov, Vladimir. Moscow Lomonosov State University. Rusia. Fil: Lukin, Sergey M. All Russian Research Institute for Organic Fertiliser and Peat. Rusia. Fil: McKenzie, Blair M. University of Dundee. Escocia. Fil: Jones, Michael. Norwegian University of Science and Technology. Noruega. Fil: Dannowski, Ralf. Leibniz Centre for Agricultural Landscape Research. Alemania. Fil: Blum, Winfried E. H. University of Natural Resources and Life Sciences. Austria. Fil: Salnjikov, Elmira. Soil Science Institute. Serbia. Fil: Saparov, Abdulla. Kazakh Research Institute of Soil Science and Agrochemistry. Kazajistán. Fil: Pachikin, Konstantin. Kazakh Research Institute of Soil Science and Agrochemistry. Kazajistán. Fil: Hennings, Volker. Büro Für Bodenfunktionsbewertung. Alemania. Fil: Scherber, Christoph. Zoological Research Museum Alexander Koenig. Alemania. Fil: Hoffmann, Jörg. Institute for Strategies and Technology Assessment, Sustainable Agriculture and Biodiversity. Alemania. Fil: Antrop, Marc. Ghent University. Bélgica. Fil: Garibaldi, Lucas A. Universidad Nacional de Río Negro. Instituto de Investigaciones en Recursos Naturales, Agroecología y Desarrollo Rural. Río Negro, Argentina. Fil: Garibaldi, Lucas A. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Recursos Naturales, Agroecología y Desarrollo Rural. Río Negro, Argentina. Fil: Gómez Carella, Dulce S. Universidad Nacional de Río Negro. Instituto de Investigaciones en Recursos Naturales, Agroecología y Desarrollo Rural. Río Negro, Argentina. Fil: Gómez Carella, Dulce S. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Recursos Naturales, Agroecología y Desarrollo Rural. Río Negro, Argentina. Fil: Augstburger, Horacio. University of Bern. Suiza. Fil: Schwilch, Gudrun. University of Bern. Suiza. Fil: Angelstam, Per. Swedish University of Agricultural Sciences. Suecia. Fil: Manton, Michael. Vytautas Magnus University. Lituania. Fil: Dronin, Nikolai M. Moscow Lomonosov State University. Rusia.

High magnetic field Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometers provide extremely high mass resolution (resolving power of ~200,000 at 400 m/z) protein detection across a broad mass range, enabling analysis of fine structure of isotopic peak clusters that is missed in other types of mass spectrometers. The protocol detailed here describes preparation of cellular extracts for purification of DNA-binding proteins using multiple chromatographic chemistries via fast protein liquid chromatography (FPLC), and identification and quantitation of the protein isoforms and their post-translational modifications by liquid chromatography coupled to Fourier transform ion cyclotron resonance mass spectrometry (LC-FT-ICR-MS). This protocol benefits from selectively purifying proteins for identification and quantitation by high resolution FT-ICR, which has the resolution to definitively distinguish between acetylation and trimethylation post-translational modification (PTM) additions.

Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background Compassionate behavior in clinicians is described as seeking to understand patients’ psychosocial, physical and medical needs, timely attending to these needs, and involving patients as they desire. The goal of our study was to evaluate compassionate behavior in patient interactions, pain management, and the informed consent process of anesthesia residents in a simulated preoperative evaluation of a patient in pain scheduled for urgent surgery. Methods Forty-nine Clinical Anesthesia residents in year 1 and 16 Clinical Anesthesia residents in year 3 from three residency programs individually obtained informed consent for anesthesia for an urgent laparotomy from a standardized patient complaining of pain. Encounters were assessed for ordering pain medication, for patient-resident interactions by using the Empathic Communication Coding System to code responses to pain and nausea cues, and for the content of the informed consent discussion. Results Of the 65 residents, 56 (86%) ordered pain medication, at an average of 4.2 min (95% CI, 3.2 to 5.1) into the encounter; 9 (14%) did not order pain medication. Resident responses to the cues averaged between perfunctory recognition and implicit recognition (mean, 1.7 [95% CI, 1.6 to 1.9]) in the 0 (less empathic) to 6 (more empathic) system. Responses were lower for residents who did not order pain medication (mean, 1.2 [95% CI, 0.8 to 1.6]) and similar for those who ordered medication before informed consent signing (mean, 1.9 [95% CI, 1.6 to 2.1]) and after signing (mean, 1.9 [95% CI, 1.6 to 2.0]; F (2, 62) = 4.21; P = 0.019; partial η2 = 0.120). There were significant differences between residents who ordered pain medication before informed consent and those who did not order pain medication and between residents who ordered pain medication after informed consent signing and those who did not. Conclusions In a simulated preoperative evaluation, anesthesia residents have variable and, at times, flawed recognition of patient cues, responsiveness to patient cues, pain management, and patient interactions.

During COP 21 in Paris 2015, several states and organizations agreed on the “4/1000” initiative for food security and climate. This initiative aims to increase world's soil organic carbon (SOC) stocks by 4‰ annually. The influence of soil development status on SOC dynamics is very important but usually not considered in studies. We analyse SOC accumulation under forest, grassland and cropping systems along a soil age gradient (10–17,000 years) to show the influence of soil development status on SOC increase. SOC stocks (0–40 cm) and accumulation rates along a chronosequence in alluvial soils of the Danube River in the Marchfeld (eastern Austria) were analysed. The analysed Fluvisols and Chernozems have been used as forest, grassland and cropland for decades or hundreds of years. The results showed that there is a fast build-up of OC stocks (0–40 cm) in young soils with accumulation of ~1.3 t ha−1 a−1 OC in the first 100 years and ~0.5 t ha−1 a−1 OC between 100 and 350 years almost independent of land use. Chernozems with a sediment deposition age older than 5.000 years have an accumulation rate Radiocarbon dating showed that the topsoil (0–10 cm) consists mainly of “>modern” and “modern” carbon indicating a fast carbon cycling. Carbon in subsoil is less exposed to decomposition and OC can be stored at long-time scales in the subsoil (14C age of 3670 ± 35 BP). In view of the ‘4/1000’ initiative, soils with constant carbon input (forest & grassland) fulfil the intended 4‰ growth rate of SOC stocks only in the first 60 years of soil development. We proclaim that under the present climate in Central Europe, the increase of SOC stocks in soil is strongly affected by the state of soil development.

Adaptive laboratory evolution (ALE) was employed to isolate arsenate and copper cross-resistant strains, from the copper-resistant M. sedula CuR1. The evolved strains, M. sedula ARS50-1 and M. sedula ARS50-2, contained 12 and 13 additional mutations, respectively, relative to M. sedula CuR1. Bioleaching capacity of a defined consortium (consisting of a naturally occurring strain and a genetically engineered copper sensitive strain) was increased by introduction of M. sedula ARS50-2, with 5.31 and 26.29% more copper recovered from enargite at a pulp density (PD) of 1 and 3% (w/v), respectively. M. sedula ARS50-2 arose as the predominant species and modulated the proportions of the other two strains after it had been introduced. Collectively, the higher Cu2+ resistance trait of M. sedula ARS50-2 resulted in a modulated microbial community structure, and consolidating enargite bioleaching especially at elevated PD.

Soil and the human gut contain approximately the same number of active microorganisms, while human gut microbiome diversity is only 10% that of soil biodiversity and has decreased dramatically with the modern lifestyle. We tracked relationships between the soil microbiome and the human intestinal microbiome. We propose a novel environmental microbiome hypothesis, which implies that a close linkage between the soil microbiome and the human intestinal microbiome has evolved during evolution and is still developing. From hunter-gatherers to an urbanized society, the human gut has lost alpha diversity. Interestingly, beta diversity has increased, meaning that people in urban areas have more differentiated individual microbiomes. On top of little contact with soil and feces, hygienic measures, antibiotics and a low fiber diet of processed food have led to a loss of beneficial microbes. At the same time, loss of soil biodiversity is observed in many rural areas. The increasing use of agrochemicals, low plant biodiversity and rigorous soil management practices have a negative effect on the biodiversity of crop epiphytes and endophytes. These developments concur with an increase in lifestyle diseases related to the human intestinal microbiome. We point out the interference with the microbial cycle of urban human environments versus pre-industrial rural environments. In order to correct these interferences, it may be useful to adopt a different perspective and to consider the human intestinal microbiome as well as the soil/root microbiome as ‘superorganisms’ which, by close contact, replenish each other with inoculants, genes and growth-sustaining molecules.

Tyrosinemia type II is a genetic disorder characterized by elevated blood levels of the amino acid tyrosine caused by the deficiency of tyrosine aminotransferase enzyme, resulting in neurologic and developmental difficulties in the patients. Although neurological sequelae are common in Tyrosinemia type II patients, the mechanisms involved are still poorly understood. The oxidative stress appears to be, at least in part, responsible for neurological complication in this inborn error metabolism. We observed that an acute injection of tyrosine in rats caused a massive oxidative stress in different brain structures. The glutathione system and superoxide dismutase enzyme are relevant antioxidant strategies of the cells and tissues, including in the brain. Other important point is the strong relation between oxidative damage and inflammatory events. Herein, we investigated the effects of chronic administration of tyrosine in the hippocampus of young rats, with emphasis in the activity of GSH related enzymes and superoxide dismutase enzyme, and the astrocytosis. We observed that rats exposed to high levels of tyrosine presented an increased content of tyrosine, which was associated with an increment in the activity of glutathione peroxidase and glutathione reductase as well as with a diminished activity of superoxide dismutase. This antioxidant imbalance was accompanied by enhanced glial fibrillary acidic protein immunoreactivity, a marker of astrocytes, in the brain area studied. In conclusion, hippocampus astrogliosis is also a characteristic of brain alteration in Tyrosinemia. In addition, the chronic exposition to high levels of tyrosine is associated with an alteration in the activity of fundamental antioxidant enzymes.

Hier wird die globale Rolle des Bodens beim Umsatz von Suswasser aufgezeigt sowie die Bedeutung der Landwirtschaft, die mehr als 70 % des gesamten weltweit verfugbaren Suswassers fur die Produktion von Lebens-und Futtermitteln sowie nachwachsenden Stoffen benotigt. Die dabei auftretenden Probleme und Losungsmoglichkeiten werden diskutiert.

Herstellung und Vermarktung von Agrarprodukten werden sowohl durch eine Veranderung von Lebensgewohnheiten und vor allem durch die Anspruche an die Ernahrung beeinflusst, wobei der Nachfrage nach tierischen Produkten wie Fleisch und Milch eine besondere Bedeutung zukommt. Die Konkurrenz um Produktionsflachen, z. B. fur die Erzeugung von Bioenergie, vor allem von Biotreibstoffen, sowie Veranderungen in der agrarischen Besitzstruktur, z. B. durch „land grabbing“, schaffen ebenfalls neue okonomische und soziale Bedingungen, die durch zusatzliche Anderungen in der Art der Vermarktung agrarischer Rohstoffe, z. B. durch spekulative Handelsformen, noch verscharft werden. Weltweite Probleme werden zusatzlich durch kriegerische Auseinandersetzungen, Bevolkerungsbewegungen und Landflucht verursacht.

Dieses Kapitel erlautert nicht nur die zahlenmasige Zunahme der Weltbevolkerung und deren raumliche Verteilung, sondern beschreibt auch die globalen Bodenverluste, z. B. durch Versiegelung und andere Formen der Bodennutzung, einschlieslich der Veranderung von Boden, z. B. infolge Kontamination durch Urbanisierung, Industrialisierung und Transport. Weitere Ausfuhrungen beschreiben ausfuhrlich die Auswirkungen der intensiven land- und forstwirtschaftlichen Nutzung, wie z. B. Bodenerosion, Bodenverdichtung, Bodenkontamination, Bodenversalzung, Verringerung der Grundwasserneubildung und Veranderung des Wasserhaushalts von Landschaften sowie die Verringerung der Biodiversitat, Erschopfung von Bodennahrstoffen und die Bildung von Treibhausgasen, mit einer abschliesenden zusammenfassenden Betrachtung der globalen Bodenveranderungen und Bodenverluste durch die Land-und Forstwirtschaft.

Um die weltweiten Nutzungsmoglichkeiten der Boden zu verstehen ist es notwendig, ihre naturlichen Eigenschaften und deren regionale Verbreitung zu kennen. Dazu werden diese weltweit auf der Basis ihrer inharenten Eigenschaften Resilienz und Produktivitat in 9 Klassen eingeteilt und ihnen unterschiedliche okologische Eigenschaften zugeordnet. Daraus kann z. B. abgeleitet werden, dass nur 12 % der Landflache der Erde, auf denen ca. 25 % der Erdbevolkerung leben, fur die Erzeugung von im Handel befindlichen wertvollen Agrarprodukten geeignet sind. Diese und weitere Daten bilden auch die Grundlage, um die Verwirklichung der nachhaltigen Entwicklungsziele der Vereinten Nationen, soweit sie die Nutzung von Boden betreffen, zu diskutieren.

Das Klima ist nicht nur ein wesentlicher Faktor der Bodenentwicklung sondern beeinflusst auch alle in und auf dem Boden ablaufenden physikalischen, chemischen und biologischen Prozesse. Diese reichen von der Freisetzung von Bodengasen, der Umsetzung organischer Stoffe, den Wachstumsbedingungen fur Pflanzen bis zur Besiedelbarkeit von Boden. Dabei besteht eine gegenseitige Beeinflussung von Klima und Boden. Dies wird an einzelnen Beispielen aufgezeigt, unter anderem auch bei der Diskussion der Frage, ob durch Speicherung von organischem Kohlenstoff im Boden durch agrarische oder forstliche Bewirtschaftung der CO2-Gehalt der Atmosphare verringert und damit der Klimawandel kontrolliert werden kann.

Die globale Verbreitung gebietsfremder und vor allem invasiver Tier- und Pflanzenarten hat sich zu einem globalen, weltumspannenden okologischen, okonomischen und sozialen Problem entwickelt, bei dem neben dem Klimawandel und der Entwicklung des Transports auch der Boden eine wichtige Rolle spielt.

Dieses Kapitel ist eine Einfuhrung in die globale Bedeutung des Bodens, sowohl fur die Bildung der Spurengase Kohlendioxid (CO2), Methan (CH4) und Di-Stickstoffoxid (N2O) und daraus resultierende okologische Prozesse einschlieslich des Klimawandels, wie auch fur die weltweite Beeinflussung der Gewasser durch die terrestrische Verwitterung und Bodenbildung, am Beispiel der Zusammensetzung der Salze der Ozeane. Daruber hinaus wird die weltweite Bedeutung des Bodens als Basis fur die Produktion von Lebens- und Futtermitteln sowie von nachwachsenden Rohstoffen und die Bereitstellung von Frischwasser und von mineralischen Rohstoffen erlautert.

A new geological epoch has begun—the Anthropocene. Huge anthropogenic transformations of terrestrial landscapes over the past five decades have forced its declaration. Exploring of interaction of humans with nature in general, and with landscapes in particular, can be characterised properly by the terms ‘landscape research’ and ‘landscape science’. Landscape science has been a traditional scientific discipline of geography. This is the case in Russia, whilst the terms geo-ecology and landscape ecology have become established in the English-speaking scientific community. As landscapes are multifunctional, highly complex systems, landscape research is a platform for disciplinary, interdisciplinary and transdisciplinary research. Landscape research in the Anthropocene must aim to combine landscape sustainability with high quality and productivity. This mission is in accord with the Sustainable Development Goals of the United Nations and the provisions of the Landscape Convention of the European Council. It includes halting landscape degradation, developing cultural landscapes and maintaining semi-natural landscapes. Clean water and air, fertile and healthy soils for food and other ecosystem services and a green and biodiverse environment are attributes of landscapes for the survival and well-being of humans in coexistence with nature. Landscape research must generate knowledge, innovations and responsible decision rules for achieving these aims. Big data gathering and scenario modelling are important for knowledge generation in a globalised world. International long-term experiments, observatories and monitoring systems will deliver data for comprehensive ecosystem models and decision support systems. Technical innovations must be imbedded in cultural solutions for the evolvement of landscapes. Springer International’s new book series ‘Innovations in Landscape Research’ aims to support better understanding, monitoring and managing landscapes. It contains a multitude of approaches and data. Some focus is on technical innovations for agri-environmental monitoring, on land and water management and its implications for landscape sustainability. Authors present novel tools for ecosystem modelling and forecasting of landscape processes, and on creating knowledge, rules and approaches for handling the multifunctionality of landscapes. The coming book series may serve as a knowledge, data and communication basis for informed decisions regarding the development of landscapes. It will enlarge our horizon and field of action by building bridges between scientific communities, scientific disciplines, and researchers and citizens.

Epigenetic phenomena have not yet been reported in archaea, which are presumed to use a classical genetic process of heritability. Here, analysis of independent lineages of Sulfolobus solfataricus evolved for enhanced fitness implicated a non-Mendelian basis for trait inheritance. The evolved strains, called super acid-resistant Crenarchaeota (SARC), acquired traits of extreme acid resistance and genome stability relative to their wild-type parental lines. Acid resistance was heritable because it was retained regardless of extensive passage without selection. Despite the hereditary pattern, in one strain, it was impossible for these SARC traits to result from mutation because its resequenced genome had no mutation. All strains also had conserved, heritable transcriptomes implicated in acid resistance. In addition, they had improved genome stability with absent or greatly decreased mutation and transposition relative to a passaged control. A mechanism that would confer these traits without DNA sequence alteration could involve posttranslationally modified archaeal chromatin proteins. To test this idea, homologous recombination with isogenic DNA was used to perturb native chromatin structure. Recombination at up-regulated loci from the heritable SARC transcriptome reduced acid resistance and gene expression in the majority of recombinants. In contrast, recombination at a control locus that was not part of the heritable transcriptome changed neither acid resistance nor gene expression. Variation in the amount of phenotypic and expression changes across individuals was consistent with Rad54-dependent chromatin remodeling that dictated crossover location and branch migration. These data support an epigenetic model implicating chromatin structure as a contributor to heritable traits.

OBJECTIVE To demonstrate the effectiveness of a Diabetes Prevention Program-inspired 12-month behavioral intervention for patients with severe mental illness (SMI) and medication-associated obesity. METHOD This randomized, controlled, parallel, superiority study screened 225 volunteers from November 2005 to August 2008 at the VA Greater Los Angeles Healthcare System. 122 outpatients with DSM-IV-diagnosed SMI taking antipsychotic medications who had ≥ 7% weight gain or body mass index (BMI) > 25 were randomized by computer-generated number to Lifestyle Balance treatment intervention (n = 60) or usual care control (n = 62) groups. Clinical raters were masked to randomization. Treatment intervention included weekly classes and individual counseling for 8 weeks, food and exercise diaries, rewards, caregiver consultations, and monthly booster classes and counseling for 1 year. Controls received self-help materials and visited at equivalent intervals without formal classes or counseling. Outcomes were changes in anthropometric measurements, psychiatric symptoms, health knowledge, and glucose, hemoglobin A1c, and lipid levels. RESULTS Our intention-to-treat analysis found significant differences in predicted trajectory of mean weight change between the groups over 12 months (P < .01), with treatment participants expected to lose an average 4.6 kg, while control participants would gain an average 0.6 kg. BMI and body fat percentage followed the same pattern. Both groups demonstrated statistically significant improvements in health knowledge quiz scores over time (P = .006), without significant difference between groups. CONCLUSIONS Treatment was more effective than usual care control in treating medication-associated obesity, independent of SMI diagnosis, antipsychotic medication, and knowledge gained, suggesting that behavioral interventions are effective in SMI patients. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT00344500.

Extremely thermoacidophilic Crenarchaeota belonging to the order Sulfolobales flourish in hot acidic habitats that are strongly oxidizing. The pH extremes of these habitats, however, often exceed the acid tolerance of type species and strains. Here, adaptive laboratory evolution was used over a 3-year period to test whether such organisms harbor additional thermoacidophilic capacity. Three distinct cell lines derived from a single type species were subjected to high-temperature serial passage while culture acidity was gradually increased. A 178-fold increase in thermoacidophily was achieved after 29 increments of shifted culture pH resulting in growth at pH 0.8 and 80°C. These strains were named super-acid-resistant Crenarchaeota (SARC). Mathematical modeling using growth parameters predicted the limits of acid resistance, while genome resequencing and transcriptome resequencing were conducted for insight into mechanisms responsible for the evolved trait. Among the mutations that were detected, a set of eight nonsynonymous changes may explain the heritability of increased acid resistance despite an unexpected lack of transposition. Four multigene components of the SARC transcriptome implicated oxidative stress as a primary challenge accompanying growth at acid extremes. These components included accelerated membrane biogenesis, induction of the mer operon, and an increased capacity for the generation of energy and reductant.