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A balanced sphingolipid rheostat is indispensable for dendritic cell function and survival and thus initiation of an immune response. Sphingolipid levels are dynamically maintained by the action of sphingolipid enzymes of which sphingosine kinases, S1P phosphatases (SGPP-1/2) and S1P lyase (SGPL-1), are pivotal in the balance of S1P and sphingosine levels. In this study, we present that SGPP-1 and SGPL-1 are regulated in inflammatory dendritic cells and contribute to S1P fate. TLR-dependent activation caused SGPL-1 protein downregulation with subsequent decrease of enzymatic activity by two-thirds. In parallel, confocal fluorescence microscopy revealed that endogenous SGPP-1 was expressed in nuclei of naive dendritic cells and was translocated into the cytoplasmatic compartment upon inflammatory stimulation resulting in dephosphorylation of S1P. Mass spectrometric determination showed that a part of the resulting sphingosine was released from the cell, increasing extracellular levels. Another route of diminishing intracellular S1P was possibly taken by its export via ATP-binding cassette transporter C1 which was upregulated in array analysis, while the S1P transporter, spinster homolog 2, was not relevant in dendritic cells. These investigations newly describe the sequential expression and localization of the endogenous S1P regulators SGPP-1 and SGPL-1 and highlight their contribution to the sphingolipid rheostat in inflammation.
Die Wahrscheinlichkeit einer pathologischen Komplettremission (pCR) bei Brustkrebs nach neoadjuvanter Chemotherapie (NACT) nimmt zu; vor allem in den Subgruppen der tripel-negativen und HER-2-positiven Tumoren. Daher stellt sich die Frage, ob bei einer Komplettremission nach NACT eine operative Therapie der Brust notwendig ist, und ob es einen Vorteil für das onkologische Behandlungsergebnis hat, wenn kein Tumor mehr nachgewiesen werden kann. Ein Verzicht auf die Operation und gegebenenfalls auch auf die Radiotherapie ist jedoch nur auf der Basis einer verlässlichen pCR-Diagnose ohne Operation denkbar. Bildgebende Verfahren erreichen derzeit nicht die nötige Sensitivität und Spezifität, um die Diagnose einer pathologischen Komplettremission sicher zu stellen. Daher sind weitere Studien nötig, um herauszufinden, welche Methode die bestmögliche Evaluation des Tumoransprechens auf NACT erlaubt. Erste vielversprechende Ergebnisse zeigen sich in Studien zu bildgebungsgesteuerten, minimalinvasiven Biopsien nach NACT. Diese evaluieren die Möglichkeit einer pCR-Diagnose vor der Operation und könnten die Grundlage für weitere Studien zu einem möglichen Verzicht auf eine Operation in diesem ausgewählten Kollektiv sein.
The likelihood of pathological complete remission (pCR) of breast cancer following neoadjuvant chemotherapy (NACT) is increasing; most of all in the triple negative and HER2 positive tumour subgroups. The question thus arises whether or not breast surgery is necessary when there is complete remission after NACT, and whether it provides any improvement of the oncological treatment result when tumour is no longer detectable. Avoiding surgery and possibly even radiotherapy would only be conceivable on the basis of a reliable diagnosis of pCR without operating. Current imaging does not achieve the necessary sensitivity and specificity to assure the diagnosis of pathological complete remission. Further studies are therefore required to determine which methods are best able to evaluate tumour response to NACT. Studies on image-guided, minimally invasive biopsies after NACT have delivered first promising results towards diagnosing pCR before surgery and could provide the basis for further studies on the possibility of avoiding surgery in this specific patient collective.
Flightless-I governs cell fate by recruiting the SUMO isopeptidase SENP3 to distinct HOX genes
(2017)
Background: Despite recent studies on the role of ubiquitin-related SUMO modifier in cell fate decisions, our understanding on precise molecular mechanisms of these processes is limited. Previously, we established that the SUMO isopeptidase SENP3 regulates chromatin assembly of the MLL1/2 histone methyltransferase complex at distinct HOX genes, including the osteogenic master regulator DLX3. A comprehensive mechanism that regulates SENP3 transcriptional function was not understood.
Results: Here, we identified flightless-I homolog (FLII), a member of the gelsolin family of actin-remodeling proteins, as a novel regulator of SENP3. We demonstrate that FLII is associated with SENP3 and the MLL1/2 complex. We further show that FLII determines SENP3 recruitment and MLL1/2 complex assembly on the DLX3 gene. Consequently, FLII is indispensible for H3K4 methylation and proper loading of active RNA polymerase II at this gene locus. Most importantly, FLII-mediated SENP3 regulation governs osteogenic differentiation of human mesenchymal stem cells.
Conclusion: Altogether, these data reveal a crucial functional interconnection of FLII with the sumoylation machinery that converges on epigenetic regulation and cell fate determination.
We have recently shown that caspase-8 is a new substrate of Polo-like kinase 3 (Plk3) that phosphorylates the protein on residue T273 thereby promoting its pro-apoptotic function. In the present study we aimed to investigate the clinical relevance of Plk3 expression and phosphorylation of caspase-8 at T273 in patients with anal squamous cell carcinoma (SSC) treated with 5-fluorouracil and mitomycin C-based chemoradiotherapy (CRT). Immunohistochemical detection of the markers was performed in pretreatment biopsy specimens of 95 patients and was correlated with clinical/histopathologic characteristics including HPV-16 virus load/p16INK4a expression and cumulative incidence of local and distant failure, cancer specific survival (CSS), and overall survival (OS). We observed significant positive correlations between Plk3 expression, pT273 caspase-8 signal, and levels of HPV-16 virus DNA load/p16INK4a detection. Patients with high scores of Plk3 and pT273 caspase-8 showed increased local control (p = 0.011; p = 0.001), increased CSS (p = 0.011; p = 0.013) and OS (p = 0.024; p = 0.001), while the levels of pT273 caspase-8 were significantly associated (p = 0.033) with distant metastases. In multivariate analyses Plk3 expression remained significant for local failure (p = 0.018), CSS (p = 0.016) and OS (p = 0.023). Moreover, a combined HPV16 DNA load and Plk3 or pT273 caspase-8 variable revealed a significant correlation to decreased local failure (p = 0.001; p = 0.009), increased CSS (p = 0.016; p = 0.023) and OS (p = 0.003; p = 0.003). In conclusion these data indicate that elevated levels of Plk3 and pT273 caspase-8 are correlated with favorable clinical outcome in patients with anal SCC treated with concomitant CRT.
Background: Aside from the fully licensed herbal medicines there are products on the European pharmaceutical market which are registered by virtue of their longstanding traditional use. The normal registration procedure does not apply to them because presently they do not meet the legal requirements for a full license as set out in the relevant European Union Directive. One of these requirements, “proof of tradition”, has so far been dealt with in different ways and fails to meet the criteria of good practice.
Method: This analysis is based on a selective literature search in PubMed and in databases of medical and pharmaceutical history, interviews with licensing experts, a consensus meeting attended by researchers with a background in general medicine, phytotherapy, medical and pharmaceutical history, biometry, ethnopharmacology, pharmacognosy and the pharmaceutical industry.
Results and discussion: The 2004 EU Directive, which governs the registration of Traditional Herbal Medicinal Products and demands proof of tradition, is a regulatory construct and, above all, the outcome of a political process that has ended in a pragmatic compromise. The concept of tradition applied in the Directive does not sufficiently reflect the semantic breadth of the term. The only condition defined is that a specific commercial preparation needs to have been on the market for 30 years (15 of them inside the EU). Such an approach does not make full scientific use of the evidence available because the information excerpted from historical sources, if adequately processed, may yield valuable insights. This applies to indications, modes of application, efficacy and product safety (innocuousness). Such criteria should enter in full into the benefit-risk-analysis of applied preparations, in the registration process as well as in the therapeutic practice.
Conclusion: When registering Traditional Herbal Medicinal Products the criterion of evidence-based medicine will only be met if all the facts available are assessed and evaluated, over and above the formally stipulated regulatory provisions (30 years, product reference). To this end, the scientific methods (from among the natural, life or cultural sciences), which are recognized as authoritative in each case, must be applied.
The paper presents a reading of "celestinesque literature" - texts surrounding Fernando de Rojas’ famous novel 'La Celestina' (1499) - in view of the question, to what extent the term "marranism" may serve as a philological rather than a biographical category. Dealing with Stephen Gilman’s exemplary studies, the paper shows how Rojas’ text subverts some of the most important metaphorical structures used by philologists to represent "marranism" and to read "marrano literature." Celestinesque novels, on the other hand, develop their own notion of "philology:" the "love" that they narrate also reflects the "desire of the logos" that works throughout their language.
"In der Machination", so Walter Benjamin, "hat die neue Bühne den Gott." Das gilt nicht nur für die Theatermaschinerie, die den Gott auf der Barockbühne erscheinen lässt, sondern ebenso für die weiteren Bedeutungen des Wortes: "Machination" im Sinn des kunstfertigen Verstands und der trügerischen List, wie sie sich in der Intrige, dem dramatischen Kern des Trauerspiels, verkörpert. Der Aufsatz entfaltet den Zusammenhang zwischen Machination und Theophanie in einem Vergleich zwischen den barocken Dichtern Gryphius und Racine. Während die Spiele des Ersteren sich vorrangig auf die anschauliche Wirkung der Maschine stützen, um die Souveränität des 'christlichen' Gesetzes zu demonstrieren, präsentieren sich die Dramen des Letzteren als Musterbeispiele für ingeniöse Handlungsführung im Namen eines Regelwerks, dessen poetologische Autorität als 'göttlich' anerkannt wird. Zwischen diesen beiden Modellen theatralen Spiels vermittelt die Analyse einer Edition der aristotelischen Poetik, die Daniel Heinsius herausgegeben hat und einen besonderen Schwerpunkt auf die Deutung des deus ex machina legt.
Der Aufsatz untersucht am Beispiel des Märtyrerspiels "Catharina von Georgien" die Charakteristik der Gryph'schen Trauerspielsprache zwischen "erhabenem Stil" und sermo humilis. Unter Rückgriff auf die einschlägigen Studien Auerbachs wird besonderes Augenmerk auf das problematische Verhältnis zwischen dem christlichen Gegenstand - der Passion als Erniedrigung des Gottessohnes - und der barocken Stillehre gelegt: Solange das Trauerspiel dem "erhabenen Stil" den Vorzug gibt, kann es das christliche Heilsgeschehen nur verfremdend wiederholen.
With reference to the martyr-play "Catharina von Georgien," my paper examines the rhetorical characteristics of Gryphius' mourning-plays as a movement between "elevated style" and sermo humilis. Drawing upon Auerbach's important studies on this subject, it highlights the problematic relationship between the play's Christian subject - the passion as humiliation of the divine Son - and baroque notions of (stylistic) elevation: As long as the mourning-play gives preference to "elevated style," it can only restage Christian salvation through its distortion.
Der Aufsatz arbeitet im Rückgriff auf Richard Alewyns bekannte Studie markante Modifikationen von Opitz' Antigone-Übersetzung auf syntaktischer, stilistischer und semantischer Ebene heraus: Während die sophokleische Tragödie vom Oxymoron geprägt ist, zeichnet sich Opitz' Übersetzung durch die Klärung des paradoxen Ausdrucks zur äußerlichen Antithese aus. Dank ihr kann die widerspruchsreiche Tragödie zum moralischen Exempel vereinfacht werden. Der Grund für diese Umdichtung wird – abweichend von Alewyn – im rhetorischen Sprachverständnis des Übersetzers gesucht: Die Eigenart seines "Teutschs" liegt in der zwiespältigen Orientierung an griechischer Tragödie und lateinischer Gerichtsrhetorik begründet. Dementsprechend kann auch die Charakteristik des "teutschen" Trauerspiels (das sich auf die griechische Tragödie beruft, aber zumeist ein religiöses Exempel statuiert) in diesem Zwiespalt einer neu zu schaffenden Trauerspielsprache verankert werden.
Der Aufsatz untersucht die Frage, inwiefern die theatrale Konstruktion von christlichen Märtyrerfiguren eine Dynamik der Konversion zum bzw. des Abfalls vom Glauben voraussetzt, die in Figuralität und Ostentation zu begründen ist. Gegenstand der Untersuchung sind die Trauerspiele 'Catharina von Georgien', 'Papinian' und 'Carolus Stuardus'.
The longevity of the population in the Okinawa Islands of Japan has been ascribed to genetic factors and the traditional Okinawa cuisine, which is low in calories and high in plant content. This diet includes shell ginger (Alpinia zerumbet (Pers.) B.L. Burtt & R.M. Sm) of the ginger family (Zingiberaceae). Due to its local popularity, Alpinia zerumbet has become the subject of a good deal of study at the University of the Ryukyus in Okinawa. Personal local experience and review of the literature now suggest that culinary shell ginger may contribute to longevity among the population in Okinawa. This is supported by its abundant phytochemical content, with antioxidant and anti-obesity properties. The major bioactive phytochemicals are dihydro-5,6-dehydrokawain (DDK; 80–410 mg g−1 fresh weight), 5,6-dehydrokawain (DK; ≤100 mg g−1), and essential oils, phenols, phenolic acids, and fatty acids (≤150 mg g−1 each). Further, Alpinia zerumbet extends the lifespan in animals by 22.6%. In conclusion, culinary shell ginger may significantly contribute to human longevity in Okinawa.
The comprehensive assessment of pain-related human phenotypes requires combinations of nociceptive measures that produce complex high-dimensional data, posing challenges to bioinformatic analysis. In this study, we assessed established experimental models of heat hyperalgesia of the skin, consisting of local ultraviolet-B (UV-B) irradiation or capsaicin application, in 82 healthy subjects using a variety of noxious stimuli. We extended the original heat stimulation by applying cold and mechanical stimuli and assessing the hypersensitization effects with a clinically established quantitative sensory testing (QST) battery (German Research Network on Neuropathic Pain). This study provided a 246 × 10-sized data matrix (82 subjects assessed at baseline, following UV-B application, and following capsaicin application) with respect to 10 QST parameters, which we analyzed using machine-learning techniques. We observed statistically significant effects of the hypersensitization treatments in 9 different QST parameters. Supervised machine-learned analysis implemented as random forests followed by ABC analysis pointed to heat pain thresholds as the most relevantly affected QST parameter. However, decision tree analysis indicated that UV-B additionally modulated sensitivity to cold. Unsupervised machine-learning techniques, implemented as emergent self-organizing maps, hinted at subgroups responding to topical application of capsaicin. The distinction among subgroups was based on sensitivity to pressure pain, which could be attributed to sex differences, with women being more sensitive than men. Thus, while UV-B and capsaicin share a major component of heat pain sensitization, they differ in their effects on QST parameter patterns in healthy subjects, suggesting a lack of redundancy between these models.
Background & Aims: Thrombopoietin receptor agonists are a new class of compounds licenced for the treatment of immune thrombocytopenic purpura. They are currently being studied for patients with thrombopenia in advanced liver disease or under therapy for hepatitis C. There are indications that the risk for development of portal vein thrombosis in patients with advanced liver cirrhosis might be increased under therapy with thrombopoietin receptor agonists. We report a case of a patient with Child class B liver cirrhosis with concurrent immune thrombocytopenic purpura that developed portal vein thrombosis under therapy with the thrombopoietin receptor agonist romiplostim.
Methods: A 50-year-old woman with hepatitis C virus associated immune thrombocytopenic purpura and Child class B liver cirrhosis presented in our emergency with rapidly evolving hydropic decompensation and general malaise. For immune thrombocytopenic purpura, the patient was started on the thrombopoietin receptor agonist romiplostim nine months ago.
Results: During hospitalization, the platelet count was measured above 330,000/μl and partial portal vein thrombosis was diagnosed by imaging studies. The thrombotic event was assumed to be associated with the romiplostim treatment for immune thrombocytopenic purpura via excessive elevation of platelet count. After anticoagulation with heparin and cessation of romiplostim treatment, complete recanalisation of the portal vein was achieved.
Conclusions: We conclude that romiplostim should be used with precaution in patients with hepatitis C-associated immune thrombocytopenic purpura and advanced liver cirrhosis as the risk for thrombotic complications may increase significantly.
The blue light-dependent interaction between the proteins iLID and Nano allows recruiting and patterning proteins on GUV membranes, which thereby capture key features of patterns observed in nature. This photoswitchable protein interaction provides non-invasive, reversible and dynamic control over protein patterns of different sizes with high specificity and spatiotemporal resolution.
European energy policy dates back to the founding days of integration, yet the emergence of supranational governance is a recent development. The article examines the extent to which European policymakers have succeeded in building up governance capacity, and what the facilitating and impeding factors were that have shaped the governance mix. The conceptual framework differentiates between orders of governance in the multilevel context, and between policy modes involving hierarchical and non-hierarchical settings and varying actor constellations. The article finds that governance capacity has emerged where second order governance (institutional and procedural rules) is concerned, while first order governance (the concrete policy process) remains the remit of national and private actors. This becomes even more obvious once the interaction between policy modes is taken into account: governance networks enhance governance capacity in the area of competition policy and agency governance; self-regulation by industry constitutes a fall-back option in case of insufficient governance capacity on cross-border issues; soft governance helps to bridge multiple policy areas and levels of governance. The article concludes that second order governance may prove effective where it combines with hierarchy but that it may fail to overcome both trade-offs between contradicting goals and resistance at lower levels.
Background: Recent studies have suggested substantial fluctuations of cognitive performance in adults both across and within days, but very little is known about such fluctuations in children. Children's sleep behavior might have an important influence on their daily cognitive resources, but so far this has not been investigated in terms of naturally occurring within-person variations in children's everyday lives.
Methods: In an ambulatory assessment study, 110 elementary school children (8–11 years old) completed sleep items and working memory tasks on smartphones several times per day in school and at home for 4 weeks. Parents provided general information about the children and their sleep habits.
Results: We identified substantial fluctuations in the children's daily cognitive performance, self-reported nightly sleep quality, time in bed, and daytime tiredness. All three facets were predictive of performance fluctuations in children's school and daily life. Sleep quality and time in bed were predictive of performance in the morning, and afternoon performance was related to current tiredness. The children with a lower average performance level showed a higher within-person coupling between morning performance and sleep quality.
Conclusions: Our findings contribute important insights regarding a potential source of performance fluctuations in children. The effect of varying cognitive resources should be investigated further because it might impact children's daily social, emotional, and learning-related functioning. Theories about children's cognitive and educational development should consider fluctuations on micro-longitudinal scales (e.g., day-to-day) to identify possible mechanisms behind long-term changes.
Compared to their protein-coding counterparts, almost nothing is known about the role of long noncoding RNAs (lncRNAs) in cardiac fibrosis. In the current report, Liang and Pan et al. characterized the pro-fibrotic lncRNA PFL in respect to cardiac fibrosis in mice. PFL was upregulated in the hearts of mice after myocardial infarction and in fibrotic cardiac fibroblasts. Moreover, PFL competitively sponged the cardio-protective miRNA let-7d in cardiac fibroblasts. Knockdown of platelet activating factor receptor (PTAFR) was shown to affect the pro-fibrotic collagen production mediated by PFL. PTAFR overexpression also led to collagen production and RNA abundance of PTAFR was also regulated by miRNA let-7d. Therefore, the PFL/PTAFR/let-7d-dependent gene regulatory mechanism proposed by the authors manifests the hypothesis of competing endogenous RNAs to cardiac fibrosis.
Structural and functional dissection of the DH and PH domains of oncogenic Bcr-Abl tyrosine kinase
(2017)
The two isoforms of the Bcr-Abl tyrosine kinase, p210 and p190, are associated with different leukemias and have a dramatically different signaling network, despite similar kinase activity. To provide a molecular rationale for these observations, we study the Dbl-homology (DH) and Pleckstrin-homology (PH) domains of Bcr-Abl p210, which constitute the only structural differences to p190. Here we report high-resolution structures of the DH and PH domains and characterize conformations of the DH–PH unit in solution. Our structural and functional analyses show no evidence that the DH domain acts as a guanine nucleotide exchange factor, whereas the PH domain binds to various phosphatidylinositol-phosphates. PH-domain mutants alter subcellular localization and result in decreased interactions with p210-selective interaction partners. Hence, the PH domain, but not the DH domain, plays an important role in the formation of the differential p210 and p190 Bcr-Abl signaling networks.
β-barrel proteins mediate nutrient uptake in bacteria and serve vital functions in cell signaling and adhesion. For the 14-strand outer membrane protein G of Escherichia coli, opening and closing is pH-dependent. Different roles of the extracellular loops in this process were proposed, and X-ray and solution NMR studies were divergent. Here, we report the structure of outer membrane protein G investigated in bilayers of E. coli lipid extracts by magic-angle-spinning NMR. In total, 1847 inter-residue 1H–1H and 13C–13C distance restraints, 256 torsion angles, but no hydrogen bond restraints are used to calculate the structure. The length of β-strands is found to vary beyond the membrane boundary, with strands 6–8 being the longest and the extracellular loops 3 and 4 well ordered. The site of barrel closure at strands 1 and 14 is more disordered than most remaining strands, with the flexibility decreasing toward loops 3 and 4. Loop 4 presents a well-defined helix.
Midkine is a pleiotropic factor, which is involved in angiogenesis. However, its mode of action in this process is still ill defined. The function of midkine in arteriogenesis, the growth of natural bypasses from pre-existing collateral arteries, compensating for the loss of an occluded artery has never been investigated. Arteriogenesis is an inflammatory process, which relies on the proliferation of endothelial cells and smooth muscle cells. We show that midkine deficiency strikingly interferes with the proliferation of endothelial cells in arteriogenesis, thereby interfering with the process of collateral artery growth. We identified midkine to be responsible for increased plasma levels of vascular endothelial growth factor A (VEGFA), necessary and sufficient to promote endothelial cell proliferation in growing collaterals. Mechanistically, we demonstrate that leukocyte domiciled midkine mediates increased plasma levels of VEGFA relevant for upregulation of endothelial nitric oxide synthase 1 and 3, necessary for proper endothelial cell proliferation, and that non-leukocyte domiciled midkine additionally improves vasodilation.
The data provided on the role of midkine in endothelial proliferation are likely to be relevant for both, the process of arteriogenesis and angiogenesis. Moreover, our data might help to estimate the therapeutic effect of clinically applied VEGFA in patients with vascular occlusive diseases.
Dysregulation of lysophosphatidic acids in multiple sclerosis and autoimmune encephalomyelitis
(2017)
Bioactive lipids contribute to the pathophysiology of multiple sclerosis. Here, we show that lysophosphatidic acids (LPAs) are dysregulated in multiple sclerosis (MS) and are functionally relevant in this disease. LPAs and autotaxin, the major enzyme producing extracellular LPAs, were analyzed in serum and cerebrospinal fluid in a cross-sectional population of MS patients and were compared with respective data from mice in the experimental autoimmune encephalomyelitis (EAE) model, spontaneous EAE in TCR1640 mice, and EAE in Lpar2 -/- mice. Serum LPAs were reduced in MS and EAE whereas spinal cord LPAs in TCR1640 mice increased during the ‘symptom-free’ intervals, i.e. on resolution of inflammation during recovery hence possibly pointing to positive effects of brain LPAs during remyelination as suggested in previous studies. Peripheral LPAs mildly re-raised during relapses but further dropped in refractory relapses. The peripheral loss led to a redistribution of immune cells from the spleen to the spinal cord, suggesting defects of lymphocyte homing. In support, LPAR2 positive T-cells were reduced in EAE and the disease was intensified in Lpar2 deficient mice. Further, treatment with an LPAR2 agonist reduced clinical signs of relapsing-remitting EAE suggesting that the LPAR2 agonist partially compensated the endogenous loss of LPAs and implicating LPA signaling as a novel treatment approach.
Objectives: The possible effects of exposure to neurotoxic substances such as gasoline, diesel fuel, paint, varnish, and solvents on the pathogenesis of obstructive sleep apnea were examined.
Methods: Four hundred and forty-three persons with incident obstructive sleep apnea were recruited within the framework of a case-referent study. A reference population (N=397) was included as the first reference group. In addition 106 patients whose sleep laboratory findings confirmed that they were not suffering from obstructive sleep apnea were then included as a second reference group. Data were gathered with a questionnaire which had to be filled out by the persons with obstructive sleep apnea (cases) and the referents themselves. In the assessment of occupational exposure the questionnaires were filled out by the subjects themselves, and a job-exposure matrix was also used. Data were analyzed using logistic regression to control for age, region, body mass index, cigarette smoking, and alcohol consumption.
Results: None of the exposures were statistically significantly associated with obstructive sleep apnea. There was no correlation with occupation. Only current activities in service occupations revealed an increased odds ratio, 1.6 (95% confidence interval 1.1-2.4).
Conclusions: No suggestion was found of an association between exposure to solvents and obstructive sleep apnea.
Renal cell carcinoma alters endothelial receptor expression responsible for leukocyte adhesion
(2016)
Renal cell carcinoma (RCC) escapes immune recognition. To elaborate the escape strategy the influence of RCC cells on endothelial receptor expression and endothelial leukocyte adhesion was evaluated. Human umbilical vein endothelial cells (HUVEC) were co-cultured with the RCC cell line, Caki-1, with and without tumor necrosis factor (TNF)-alpha. Intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), endothelial (E)-selectin, standard and variants (V) of CD44 were then analysed in HUVEC, using flow cytometry and Western blot analysis. To determine which components are responsible for HUVEC-Caki-1 interaction causing receptor alteration, Caki-1 membrane fragments versus cell culture supernatant were applied to HUVECS. Adhesion of peripheral blood lymphocytes (PBL) and polymorphonuclear neutrophils (PMN) to endothelium was evaluated by co-culture adhesion assays. Relevance of endothelial receptor expression for adhesion to endothelium was determined by receptor blockage. Co-culture of RCC and HUVECs resulted in a significant increase in endothelial ICAM-1, VCAM-1, E-selectin, CD44 V3 and V7 expression. Previous stimulation of HUVECs with TNF-alpha and co-cultivation with Caki-1 resulted in further elevation of endothelial CD44 V3 and V7 expression, whereas ICAM-1, VCAM-1 and E-selectin expression were significantly diminished. Since Caki-1 membrane fragments also caused these alterations, but cell culture supernatant did not, cell-cell contact may be responsible for this process. Blocking ICAM-1, VCAM-1, E-selectin or CD44 with respective antibodies led to a significant decrease in PBL and PMN adhesion to endothelium. Thus, exposing HUVEC to Caki-1 results in significant alteration of endothelial receptor expression and subsequent endothelial attachment of PBL and PMN.
Regulation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor trafficking in response to neuronal activity is critical for synaptic function and plasticity. Here, we show that neuronal activity induces the binding of ephrinB2 and ApoER2 receptors at the postsynapse to regulate de novo insertion of AMPA receptors. Mechanistically, the multi-PDZ adaptor glutamate-receptor-interacting protein 1 (GRIP1) binds ApoER2 and bridges a complex including ApoER2, ephrinB2, and AMPA receptors. Phosphorylation of ephrinB2 in a serine residue (Ser-9) is essential for the stability of such a complex. In vivo, a mutation on ephrinB2 Ser-9 in mice results in a complete disruption of the complex, absence of ApoER2 downstream signaling, and impaired activity-induced and ApoER2-mediated AMPA receptor insertion. Using compound genetics, we show the requirement of this complex for long-term potentiation (LTP). Together, our findings uncover a cooperative ephrinB2 and ApoER2 signaling at the synapse, which serves to modulate activity-dependent AMPA receptor dynamic changes during synaptic plasticity.
Checkpoint kinase inhibitor AZD7762 strongly sensitises urothelial carcinoma cells to gemcitabine
(2017)
Background: More effective chemotherapies are urgently needed for bladder cancer, a major cause of morbidity and mortality worldwide. We therefore explored the efficacy of the combination of gemcitabine and AZD7762, a checkpoint kinase 1/2 (CHK1/2) inhibitor, for bladder cancer.
Methods: Viability, clonogenicity, cell cycle distribution and apoptosis were assessed in urothelial cancer cell lines and various non-malignant urothelial cells treated with gemcitabine and AZD7762. DNA damage was assessed by γH2A.X and 53-BP1 staining and checkpoint activation was followed by Western blotting. Pharmacological inhibition of CHK1 and CHK2 was compared to downregulation of either CHK1 or CHK2 using siRNAs.
Results: Combined use of gemcitabine and AZD7762 synergistically reduced urothelial carcinoma cell viability and colony formation relative to either single treatment. Non-malignant urothelial cells were substantially less sensitive to this drug combination. Gemcitabine plus AZD7762 inhibited cell cycle progression causing cell accumulation in S-phase. Moreover, the combination induced pronounced levels of apoptosis as indicated by an increase in the fraction of sub-G1 cells, in the levels of cleaved PARP, and in caspase 3/7 activity. Mechanistic investigations showed that AZD7762 treatment inhibited the repair of gemcitabine-induced double strand breaks by interference with CHK1, since siRNA-mediated depletion of CHK1 but not of CHK2 mimicked the effects of AZD7762.
Conclusions: AZD7762 enhanced sensitivity of urothelial carcinoma cells to gemcitabine by inhibiting DNA repair and disturbing checkpoints. Combining gemcitabine with CHK1 inhibition holds promise for urothelial cancer therapy.
Purpose: Few individuals that are latently infected with M. tuberculosis latent tuberculosis infection(LTBI) progress to active disease. We investigated risk factors for LTBI and active pulmonary tuberculosis (PTB) in Germany.
Methods: Healthy household contacts (HHCs), health care workers (HCWs) exposed to M. tuberculosis and PTB patients were recruited at 18 German centres. Interferon-γ release assay (IGRA) testing was performed. LTBI risk factors were evaluated by comparing IGRA-positive with IGRA-negative contacts. Risk factors for tuberculosis were evaluated by comparing PTB patients with HHCs.
Results: From 2008–2014, 603 HHCs, 295 HCWs and 856 PTBs were recruited. LTBI was found in 34.5% of HHCs and in 38.9% of HCWs. In HCWs, care for coughing patients (p = 0.02) and longstanding nursing occupation (p = 0.04) were associated with LTBI. In HHCs, predictors for LTBI were a diseased partner (odds ratio 4.39), sexual contact to a diseased partner and substance dependency (all p < 0.001). PTB was associated with male sex, low body weight (p < 0.0001), alcoholism (15.0 vs 5.9%; p < 0.0001), glucocorticoid therapy (7.2 vs 2.0%; p = 0.004) and diabetes (7.8 vs. 4.0%; p = 0.04). No contact developed active tuberculosis within 2 years follow-up.
Conclusions: Positive IGRA responses are frequent among exposed HHCs and HCWs in Germany and are poor predictors for the development of active tuberculosis.
Measuring NADPH oxidase (Nox)-derived reactive oxygen species (ROS) in living tissues and cells is a constant challenge. All probes available display limitations regarding sensitivity, specificity or demand highly specialized detection techniques. In search for a presumably easy, versatile, sensitive and specific technique, numerous studies have used NADPH-stimulated assays in membrane fractions which have been suggested to reflect Nox activity. However, we previously found an unaltered activity with these assays in triple Nox knockout mouse (Nox1-Nox2-Nox4-/-) tissue and cells compared to wild type. Moreover, the high ROS production of intact cells overexpressing Nox enzymes could not be recapitulated in NADPH-stimulated membrane assays. Thus, the signal obtained in these assays has to derive from a source other than NADPH oxidases. Using a combination of native protein electrophoresis, NADPH-stimulated assays and mass spectrometry, mitochondrial proteins and cytochrome P450 were identified as possible source of the assay signal. Cells lacking functional mitochondrial complexes, however, displayed a normal activity in NADPH-stimulated membrane assays suggesting that mitochondrial oxidoreductases are unlikely sources of the signal. Microsomes overexpressing P450 reductase, cytochromes b5 and P450 generated a NADPH-dependent signal in assays utilizing lucigenin, L-012 and dihydroethidium (DHE). Knockout of the cytochrome P450 reductase by CRISPR/Cas9 technology (POR-/-) in HEK293 cells overexpressing Nox4 or Nox5 did not interfere with ROS production in intact cells. However, POR-/- abolished the signal in NADPH-stimulated assays using membrane fractions from the very same cells. Moreover, membranes of rat smooth muscle cells treated with angiotensin II showed an increased NADPH-dependent signal with lucigenin which was abolished by the knockout of POR but not by knockout of p22phox. In conclusion: the cytochrome P450 system accounts for the majority of the signal of Nox activity chemiluminescence based assays.
Since the introduction of radiological examination techniques, such as an angiographic computed tomography (ACT) and a computed tomographic angiography (CTA), the diagnosis and treatment planning for cerebral aneurysms became quicker and safer. Unfortunately, the state of development of these techniques, and their possible indications and benefits are still today restricted to specialized centers. The objective of this update was to analyze the current scientific evidence about their actual interventional and diagnostic use and identify the individual advantages of each through a literature review and personal experience-based data.
Planted forests of alien tree species make significant contributions to the economy and provide multiple products and ecosystem services On the other hand, non-native trees now feature prominently on the lists of invasive alien plants in many parts of the world, and in some areas non-native woody species are now among the most conspicuous, damaging and, in some cases, best-studied invasive species. Afforestation and reforestation policies, both on public and private land, need to include clearly stated objectives and principles to reduce impacts of invasive trees outside areas set aside for forestry. With the intention of encouraging national authorities to implement general principles of prevention and mitigation of the risks posed by invasive alien tree species used in plantation forestry into national environmental policies, the Council of Europe facilitated the preparation of a Code of Conduct on Planted Forest and Invasive Alien Trees. This new voluntary Code, comprising 14 principles, complements existing codes of conduct dealing with horticulture and botanic gardens. The Code is addressed to all relevant stakeholders and decision makers in the 47 Member States of the Council of Europe. It aims to enlist the co-operation of the forest sector (trade and industry, national forest authorities, certification bodies and environmental organizations) and associated professionals in preventing new introductions and reducing, controlling and mitigating negative impacts due to tree invasions that arise, directly or indirectly, as a consequence of plantation forestry.
Cat’s claw creeper vine, Dolichandra unguis-cati (L.) Lohmann (syn. Macfadyena unguis-cati (L.) Gentry) (Bignoniaceae), is a major environmental weed in Australia. Two distinct forms of this weed (‘long’ and ‘short’ pod), with differences in leaf morphology and fruit size, occur in Australia. The long pod form has only been reported in less than fifteen localities in the whole of south-east Queensland, while the short pod form is widely distributed in Queensland and New South Wales. This study sought to compare growth traits such as specific leaf area, relative growth rate, stem length, shoot/root ratio, tuber biomass and branching architecture between these forms. These traits were monitored under glasshouse conditions over a period of 18 months. Short pod exhibited higher values of relative growth rates, stem length, number of tubers and specific leaf area than long pod, but only after 10 months of plant growth. Prior to this, long and short pod did not differ significantly. Higher values for these traits have been described as characteristics of successful colonizers. Results from this study could partly explain why the short pod form is more widely distributed in Australia while long pod is confined to a few localities.
The 13th International Conference on Ecology and Management of Alien Plant Invasions (EMAPi) was held in Waikoloa Village, Hawaii, 20–24 September 2015. EMAPi is the only international conference that focuses exclusively on alien plants; its history and broad significance were outlined by Richardson et al. (2010). During EMAPi 2015, over 200 presentations were delivered by delegates hailing from 31 countries. The presentations covered a wide range of topics in invasion biology, addressing organizational levels ranging from the gene to global patterns. Connecting science with management emerged as a unifying theme across the conference program. Commonalities emerged through lively discussions, giving new insights into research needs, management strategies, and more effective implementation of biosecurity and control. A highlight was the mid-conference field trip, where researchers, land managers, and policy makers discussed collaboration and solutions in the stimulating back drop of Hawaii Volcanoes National Park, Hakalau National Wildlife Refuge, and other conservation sites that have evolving invasive plant management strategies.
Biological control of weeds in Vanuatu began in 1935, with the introduction of the tingid Teleonemia scrupulosa to control Lantana camara. To date, nine biological control agents have been intentionally introduced to control eight weed species. Seven of these agents have established on their respective hosts while an eighth, Zygogramma bicolorata, an agent for Parthenium hysterophorus has only recently been released and establishment is unlikely. The fate of a ninth agent, Heteropsylla spinulosa, released for the control of Mimosa diplotricha is unclear. Six other biological control agents, including Epiblema strenuana which was first detected in 2014 on P. hysterophorus on Efate have spread into the country unintentionally. Control of the target weeds range from inadequate to very good. By far the most successful agent has been Calligrapha pantherina which was introduced to control Sida acuta and Sida rhombifolia. The beetle was released on 14 islands and managed to spread to at least another 10 islands where it has effectively controlled both Sida spp. Control of the two water weeds, Eichhornia crassipes by Neochetina bruchi and N. eichhorniae and Pistia stratiotes by Neohydronomus affinis, has also been fairly good in most areas. Two agents, T. scrupulosa and Uroplata girardi, were released on L. camara, and four other agents have been found on the weed, but L. camara is still not under adequate control. The rust Puccinia spegazzinii was first released on Mikania micrantha in 2012 and successfully established. Anecdotal evidence suggests that it is having an impact on M. micrantha, but detailed monitoring is required to determine its overall impact. Future prospects for weed biological control in Vanuatu are positive, with the expected greater spread of recently released agents and the introduction of new agents for P. hysterophorus, L. camara, Dolichandra unguis-cati and Spathodea campanulata.
Biological control of introduced weeds in the 22 Pacific island countries and territories (PICTs) began in 1911, with the lantana seed-feeding fly introduced into Fiji and New Caledonia from Hawaii. To date, a total of 62 agents have been deliberately introduced into the PICTs to control 21 weed species in 17 countries. A further two agents have spread naturally into the region. The general impact of the 36 biocontrol agents now established in the PICTs ranges from none to complete control of their target weed(s). Fiji has been most active in weed biocontrol, releasing 30 agents against 11 weed species. Papua New Guinea, Guam, and the Federated States of Micronesia have also been very active in weed biocontrol. For some weeds such as Lantana camara, agents have been released widely, and can now be found in 15 of the 21 PICTs in which the weed occurs. However, agents for other commonly found weeds, such as Sida acuta, have been released in only a few countries in which the weed is present. There are many safe and effective biocontrol agents already in the Pacific that could be utilised more widely, and highly effective agents that have been released elsewhere in the world that could be introduced following some additional host specificity testing. This paper discusses the current status of biological control efforts against introduced weeds in the 22 PICTs and reviews options that could be considered by countries wishing to initiate weed biological control programmes.
Successful invasion is often due to a combination of species characteristics (or invasiveness) and habitat suitability (or invasibility). Our objective was to identify preferred habitats and suitable environmental conditions for the African tulip tree Spathodea campanulata (Bignoniaceae), one of the most invasive alien trees on the tropical island of French Polynesia (South Pacific Ocean), in relation to its distribution and photosynthesis capacity. Spathodea abundance and leaf chlorophyll fluorescence Fo’, ETRmax, and Y(II) effective were examined in relation to topography and micro-climate along elevational transects between 140 m and 1,300 m. Results showed that Spathodea is (1) present up to 1,240 m with lowest maximum July–October (cool season) temperature of 9.4 °C and an average July-October temperature of 14.6 °C, (2) is able to colonize slope steepness of more than 45°, (3) is well represented in the elevational range of 140–540 m as well as in the native forests between 940 m and 1,040 m, suggesting a high threat for native and endemic plants species. Along one of the transects, in the elevation range of 541–940 m, Spathodea was under-represented, Chl fluorescence Fo’ increased significantly while Y(II)effective decreased significantly supporting the hypothesis that this range is a non-preferred environment, probably due to microclimate conditions characterized by punctual air dryness. Among Spathodea plants surveyed along a wetter transect, Y(II)effective and ETRmax were comparable from low elevation to mid-high elevation indicating that the potential photosynthesis rate of Spathodea may be similar from sea level until mid-high elevation. Major infestations on the island of Tahiti were reported on the leeward (drier and urbanized) west coast, but Spathodea has also been recently found on the slopes of the windward (wetter) east coast. Chlorophyll fluorescence measurements indicate a high photosynthetic capacity among Spathodea in wet environments suggesting that Spathodea will become invasive across most of the island of Tahiti.
The annual grass Bromus tectorum has invaded millions of hectares in western North America and has transformed former perennial grass and shrub-dominated communities into annual grasslands. Fire plays a key role in the maintenance of B. tectorum on the landscape but the type of disturbance responsible for initial invasion is less well understood. We conducted an experiment in a perennial shrub/grass/forb community in eastern Idaho, USA to examine the roles of plant community and soil disturbance on B. tectorum emergence and establishment prior to state-changing fires. Our experiment consisted of a plant community disturbance treatment where we (1) removed the shrub component, (2) removed the grass/forb component, or (3) removed all shrubs, grasses, and forbs. We followed this treatment with seeding of B. tectorum onto the soil surface that was (1) intact, or (2) disturbed. Each experimental plot had an associated control with no plant community disturbance but was seeded in the same manner. The experiment was replicated 20 times in two sites (high and low aboveground biomass). We measured emergence by counting seedlings in late spring and establishment by counting, removing, and weighing B. tectorum individuals in mid-summer. We also examined the influence of plant community disturbance on the soil environment by measuring extractable NH4 + and NO3 – four times each summer. Soil disturbance greatly influenced the number of B. tectorum individuals that emerged each spring. Plant community disturbance, specifically disturbance of the grass/forb component, increased N availability in the late growing season and biomass of B. tectorum the following summer. We conclude that soil disturbance and plant community disturbance interact to promote the initial invasion of B. tectorum in Intermountain West valley ecosystems.
Many recent studies in invasion science have identified species traits that determine either invasiveness or impact. Such analyses underpin risk assessments and attempts to prioritise management actions. However, the factors that mediate the capacity of an introduced species to establish and spread (i.e. its invasiveness) can differ from those that affect the nature and severity of impacts. Here we compare those traits correlated with invasiveness with those correlated with impact for Cactaceae (“cacti”) in South Africa. To assess impact magnitude, we scored 70 cacti (35 invasive and 35 non-invasive species) using the Generic Impact Scoring System (GISS) and identified traits correlated with impact using a decision tree approach. We then compared the traits correlated with impact with those identified in a recent study as correlated with invasiveness (i.e. native range size and growth form). We found that there is a significant correlation between native range size and both invasiveness and impact. Cacti with larger native ranges were more likely to become invasive (p=0.001) and cause substantial impacts (p=0.01). These results are important for prioritising efforts on the management of cactus species. Understanding when and why impact and invasiveness are correlated (as they appear to be for Cactaceae) is likely to be an important area of future research in risk assessment.
The risk of introducing weeds to new areas through grain (cereals, oilseeds and pulses) intended for processing or consumption is typically considered less than that from seed or plants for planting. However, within the range of end uses for grain, weed risk varies significantly and should not be ignored. In this paper, we discuss pathway risk analysis as a framework to examine the association of weed seeds with grain commodities throughout the production process from field to final end use, and present inspection sampling data for grain crops commonly imported to Canada. In the field, weed seed contamination of grain crops is affected by factors such as country of origin, climate, biogeography and production and harvesting practices. As it moves toward export, grain is typically cleaned at a series of elevators and the effectiveness and degree of cleaning are influenced by grain size, shape and density as well as by grade requirements. In cases where different grain lots are blended, uncertainty may be introduced with respect to the species and numbers of weed seed contaminants. During transport and storage, accidental spills and cross-contamination among conveyances may occur. At the point of import to Canada, inspection sampling data show that grain shipments contain a variety of contaminants including seeds of regulated weeds and species that represent new introductions. However, grain cleaning and processing methods tailored to end use at destination also affect the presence and viability of weed seeds. For example, grains that are milled or crushed for human use present a lower risk of introducing weed seeds to new environments than grains that undergo minimal or no processing for livestock feed, or screenings that are produced as a by-product of grain cleaning. Pathway risk analysis allows each of these stages to be evaluated in order to characterize the overall risk of introducing weeds with particular commodities, and guide regulatory decisions about trade and plant health.
Like most jurisdictions, Australia is managing a broad range of invasive alien species. Here, we provide the first holistic quantification of how much invasive species impact Australia’s economy, and how much Australia spends on their management. In the 01–02 financial year (June to July), the combined estimated cost (economic losses and control) of invasive species was $9.8 billion, rising to $13.6 billion in the 11–12 financial year. Approximately $726 million of grants funded through the Commonwealth of Australia (i.e. federal funding) was spent on invasive species management and research between 1996 to 2013. In 01–02, total national expenditure on invasive species was $2.31 billion, rising to $3.77 billion in 11–12. Agriculture accounted for more than 90% of the total cost. For 01–02 and 11–12, these expenditure figures equate to $123 and $197 per person per year respectively, as well as 0.32 and 0.29% of GDP respectively. All values provided here are most likely to be underestimates of the real values due to the significant constraints of the data obtainable. Invasive species are clearly a significant economic burden in Australia. Given the extent of the issue of invasive species globally, there is a clear need for better quantifications of both economic loss and expenditure in more jurisdictions, as well as in Australia.
In our recent Discussion paper, we presented our view that the only real distinction between biological invasions and natural colonisations is the human element. We agree that invasion science is a very important science, not only to better understand the role that human mediation plays for colonisation, but also for many other science fields. We agree with all invasion researchers that the human influence can result in spectacular differences, including in rates of species movement, rates of successful colonisation, the particular species being moved, the biogeography of dispersal pathways and rates of any resulting ecological disturbance and biodiversity loss. Our deep point is that that species dispersed by human-mediation or natural colonisation are all subject to the same basic laws and rules of ecology, identical to many other phenomenon that occur naturally and can be greatly influenced by people. The human dimension is merely a mechanistic distinction, albeit important because it exposes insights about the colonisation process that cannot be seen by the study of natural colonisations alone. We provide 10 hypotheses that can be scientifically tested to determine whether biological invasions and natural colonisations are two separate processes or the same process being influenced by different mechanisms.
The authors inserted an incorrect figure in Oswalt et al. (2015) that was printed as Fig. 2. The mapped species represented in Oswalt et al. (2015) is Triadica sebifera or Chinese tallow. The correct Fig. 2, representing Imperata cylindrica, is reproduced below. The correction does not alter the conclusions of Oswalt et al. (2015).
Since first of January 2015, the EU-regulation 1143/2014 obligates all member states to conduct costbenefit analyses in preparation of control programs for invasive alien species to minimize and mitigate their impacts. In addition, with ratification of the Rio Declaration and the amended Federal Nature Conservation Act, Germany is committed to control any further spread of invasive species. This is the first cost-benefit analysis estimating positive welfare effects and societal importance of H. mantagezzianum invasion control in Germany. The paper analyses possible control options limiting stands of giant hogweeds (H. mantegazzianum) based on survey data of n = 287 German districts. We differentiate between several control options (e.g. root destruction, mechanical cutting or mowing, chemical treatment and grazing) depending on infested area size and protection status. The calculation of benefits is based on stated preference results (choice experiment; n = 282). For the cost side, we calculate two different invasion scenarios (i) no re-infestation after successfully conducted control measures (optimistic) and (ii) re-infestation twice after conducting control measures occurring within ten years (pessimistic). Minimum costs of eradication measures including a time span of ten years and a social discount rate of 1% result in a total of 3,467,640 € for optimistic scenario and 6,254,932 € for pessimistic invasion scenario, where no success of the first eradication attempt is assumed. Benefits of invasion control in Germany result in a total of 238,063,641 € per year and overassessment-factor corrected in 59,515,910 € per year.
The management of invasive alien species (IAS) in protected areas has become increasingly important in recent years. In this study, we analyse IAS management in the bilateral National Park Thayatal-Podyjí at the Austrian-Czech border. Based on two surveys from the years 2001 and 2010 and on annual management data from 2001-2010 we analyse changes in distribution and the efficiency of IAS management of three invasive alien plants (Fallopia × bohemica, Impatiens glandulifera, Robinia pseudoacacia). In 2010, the three study species had invaded 161 ha (2%) of the study area. Despite a decade of management, F. × bohemica has become widespread, whereas I. glandulifera distribution has decreased strongly. The most widespread species, R. pseudoacacia, has declined substantially in cover, but the area invaded has increased. From 2001 to 2010, annual management effort declined by about half. Management effort per hectare and decade was highest for F. × bohemica (2,657 hours), followed by R. pseudoacacia (1,473 hours) and I. glandulifera (270 hours). Management effort for achieving the same amount of reduction in population size and cover was highest for R. pseudoacacia, followed by F. × bohemica and I. glandulifera. We conclude that substantial effort and resources are necessary to successfully manage the study species and have to be provided over prolonged time periods, and thus continued management of these species is recommended. We highly recommend a systematic approach for monitoring the efficiency of IAS management projects in protected areas.
In a recent Discussion Paper, Hoffmann and Courchamp (2016) posed the question: are biological invasions and natural colonisations that different? This apparently simple question resonates at the core of the biological study of human-induced global change, and we strongly believe that the answer is yes: biological invasions and natural colonisations differ in processes and mechanisms in ways that are crucial for science, management, and policy. Invasion biology has, over time, developed into the broader transdisciplinary field of invasion science. At the heart of invasion science is the realisation that biological invasions are not just a biological phenomenon: the human dimension of invasions is a fundamental component in the social-ecological systems in which invasions need to be understood and managed.
The Anthropocene Epoch is characterized by novel and increasingly complex dependencies between the environment and human civilization, with many challenges of biodiversity management emerging as wicked problems. Problems arising from the management of biological invasions can be either tame (with simple or obvious solutions) or wicked, where difficulty in appropriately defining the problem can make complete solutions impossible to find. We review four case studies that reflect the main goals in the management of biological invasions – prevention, eradication, and impact reduction – assessing the drivers and extent of wickedness in each. We find that a disconnect between the perception and reality of how wicked a problem is can profoundly influence the likelihood of successful management. For example, managing species introductions can be wicked, but shifting from species-focused to vector-focused risk management can greatly reduce the complexity, making it a tame problem. The scope and scale of the overall management goal will also dictate the wickedness of the problem and the achievability of management solutions (cf. eradication and ecosystem restoration). Finally, managing species that have both positive and negative impacts requires engagement with all stakeholders and scenario-based planning. Effective management of invasions requires either recognizing unavoidable wickedness, or circumventing it by seeking alternative management perspectives.
In Niedersachsen sind etwa 50 % der forstlichen Standorte in einem Maßstab 1 : 25 000 nach einem relativ komplexen Verfahren kartiert. Jede kartierte Einheit besteht aus Stufen für den Geländewasserhaushalt (WHZ; 43 Stufen), die Nährstoffversorgung (NZ; 16 Stufen) und die Substratund Lagerungsverhältnisse (SLZ; 105 Stufen). Das Ziel der Arbeit war es, WHZ und NZ Stufen der Niedersächsischen forstlichen Standortskartierung für nicht kartierte Gebiete vorherzusagen. Anhand von stratifizierten Zufallsstichproben der WHZ und NZ Stufen aus der Kartierung wurden zwei RandomForest-Modelle kalibriert. Das Modell klassifizierte etwa 77 % der Teststichprobe für die WHZ richtig. Die F1-Werte der einzelnen Stufen reichten dabei von 50–95 %. Falsche Vorhersagen mehrten sich bei Übergängen benachbarter WHZ (z. B. Übergang von Tälern zu Hängen) und bei WHZ mit ähnlichen Geländeeigenschaften, aber Abstufungen in der Wasserversorgung. Einige Modellfehler hängen aber offenbar auch von Unschärfen innerhalb der zugrundeliegenden Kartierung ab. Zusätzlich sagt das Modell im Vergleich zur Feldkartierung viel kleinräumigere Muster vorher, die zwar vom zugrundeliegenden Gelände her nachvollziehbar erscheinen, aber in dieser Genauigkeit nicht im Feld kartiert werden. Etwa 66 % des Testdatensatzes für die NZ wurden richtig klassifiziert. Falsche Vorhersagen traten hier vor allem in direkt benachbarten Stufen der Nährstoffversorgung auf. Unsicherheiten deuten zum einen auf weniger gut geeignete Kovariablen hin, sind möglicherweise aber auch durch zeitliche Änderungen der Bodeneigenschaften selbst sowie durch Ungenauigkeiten in der Kartierung zu erwarten, die wenige Regeln für die Vergabe der Nährstoffzahl vorgibt. Insgesamt beurteilen wir die Modelle als gut geeignet, um sie landesweit anzuwenden. Allerdings ist zu erwarten, dass eine lokale Kalibrierung der Modelle für einzelne Wuchsgebiete die Modellgüte deutlich erhöht. Gleiches kann eine Zusammenfassung ähnlicher Stufen zu waldbaulich relevanten Obergruppen leisten.
Ableitung von Leitbodenprofilen für die Punkte der Bundeswaldinventur in Sachsen und Thüringen
(2016)
Die Bundeswaldinventur (BWI) ist als Stichprobenverfahren zur Erhebung der Daten von Waldfläche und Baumartenverteilung sowie Holzzuwachs und Holzvorrat etabliert. Um das Wachstum der Bäume besser beschreiben, erklären und vorhersagen zu können, werden neben anderen Standortsfaktoren Bodeninformationen an den Traktecken dieser Inventurpunkte benötigt. Im Rahmen dieser Publikation wird die Ableitung der Leitprofile zur Charakterisierung des Bodens am BWI-Punkt aus Weiserprofilen der Standortserkundung für Sachsen und Thüringen aufgezeigt. An 81 % der sächsischen und 87 % der thüringischen Traktecken konnten Leitprofile mit vollständigen bodenphysikalischen Eigenschaften zugeordnet werden. Diese umfassen die Horizontabfolge in der Tiefe, für jeden Horizont die Horizontbezeichnung, Sand-, Schluff- und Tongehalte, Skelettgehalte, Angaben zur Trockenrohdichte, zum Stau- und Grundwassereinfluss sowie zu Geologie und Schichtung. Die Standortsverhältnisse an den Traktecken, als Stichprobe der kartierten Waldfläche, sind repräsentativ für die landesweiten Verhältnisse. Die aus der Methodik resultierenden Unsicherheiten konnten beispielhaft quantifiziert werden und erwiesen sich als akzeptabel. Es hat sich gezeigt, dass die Ergebnisse der Aggregierung zu Leitprofilen recht robust gegenüber verschiedenen Aggregierungsansätzen sind. Damit ist es möglich, für die Traktecken der BWI Kenngrößen des Wasserhaushaltes zu berechnen, diese für die Standorts-Leistungs-Modellierung zu nutzen und damit das Waldwachstum besser zu beschreiben, zu erklären und zu prognostizieren.