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Background: Recurrent airway infections are common in patients with Down’s syndrome (DS). Hence, ruling out Cystic Fibrosis (CF) in these patients is often required. In the past, the value of sweat testing – the gold standard to diagnose CF – has been questioned in DS as false positive results have been reported. However, these reports are based on measurements of sweat osmolality or sodium concentrations, not chloride concentrations. This study analyses sweat secretion rate and chloride concentration in sweat samples of patients with DS in comparison to healthy controls.
Methods: We assessed sweat samples in 16 patients with DS and 16 healthy controls regarding sweat secretion rate (SSR) and sweat chloride concentration.
Results: All measured chloride concentrations were within the normal range. The chloride concentrations were slightly, but not significantly lower in patients with DS (15,54 mmol/l (±4,47)) compared to healthy controls (18,31 mmol/l (±10,12)). While no gender gap in chloride concentration could be found, chloride concentration increased with age in both groups.
Insufficient sweat was collected in 2 females with DS (12.5% of the study group) but not in an individual of the control group. A significant lower sweat secretion rate was found in the DS group (27,6 μl/30 min (± 12,18)) compared to the control group (42,7 μl/30 min (± 21,22)). In a sub-analysis, female patients produced significantly less sweat (20,8 ± 10,6 μl/30 min) than male patients with DS (36,4 ± 7,8 μl/30 min), which accounts for the difference between patients and controls. Furthermore, while the sweating secretion rate increased with age in the control group, it did not do so in the DS group. Once again this was due to female patients with DS, who did not show a significant increase of sweat secretion rate with age.
Conclusions: Sweat chloride concentrations were within the normal range in patients with DS and therefore seem to be a reliable tool for testing for CF in these patients. Interestingly, we found a reduced sweat secretion rate in the DS group. Whether the last one has a functional and clinical counterpart, possibly due to a disturbed thermoregulation in DS patients, requires further investigation.
Membrane proteins frequently assemble into higher order homo- or hetero-oligomers within their natural lipid environment. This complex formation can modulate their folding, activity as well as substrate selectivity. Non-disruptive methods avoiding critical steps, such as membrane disintegration, transfer into artificial environments or chemical modifications are therefore essential to analyze molecular mechanisms of native membrane protein assemblies. The combination of cell-free synthetic biology, nanodisc-technology and non-covalent mass spectrometry provides excellent synergies for the analysis of membrane protein oligomerization within defined membranes. We exemplify our strategy by oligomeric state characterization of various membrane proteins including ion channels, transporters and membrane-integrated enzymes assembling up to hexameric complexes. We further indicate a lipid-dependent dimer formation of MraY translocase correlating with the enzymatic activity. The detergent-free synthesis of membrane protein/nanodisc samples and the analysis by LILBID mass spectrometry provide a versatile platform for the analysis of membrane proteins in a native environment.
A primordial state of matter consisting of free quarks and gluons that existed in the early universe a few microseconds after the Big Bang is also expected to form in high-energy heavy-ion collisions. Determining the equation of state (EoS) of such a primordial matter is the ultimate goal of high-energy heavy-ion experiments. Here we use supervised learning with a deep convolutional neural network to identify the EoS employed in the relativistic hydrodynamic simulations of heavy ion collisions. High-level correlations of particle spectra in transverse momentum and azimuthal angle learned by the network act as an effective EoS-meter in deciphering the nature of the phase transition in quantum chromodynamics. Such EoS-meter is model-independent and insensitive to other simulation inputs including the initial conditions for hydrodynamic simulations.
Background: Agrocybe aegerita is an agaricomycete fungus with typical mushroom features, which is commercially cultivated for its culinary use. In nature, it is a saprotrophic or facultative pathogenic fungus causing a white-rot of hardwood in forests of warm and mild climate. The ease of cultivation and fructification on solidified media as well as its archetypal mushroom fruit body morphology render A. aegerita a well-suited model for investigating mushroom developmental biology.
Results: Here, the genome of the species is reported and analysed with respect to carbohydrate active genes and genes known to play a role during fruit body formation. In terms of fruit body development, our analyses revealed a conserved repertoire of fruiting-related genes, which corresponds well to the archetypal fruit body morphology of this mushroom. For some genes involved in fruit body formation, paralogisation was observed, but not all fruit body maturation-associated genes known from other agaricomycetes seem to be conserved in the genome sequence of A. aegerita. In terms of lytic enzymes, our analyses suggest a versatile arsenal of biopolymer-degrading enzymes that likely account for the flexible life style of this species. Regarding the amount of genes encoding CAZymes relevant for lignin degradation, A. aegerita shows more similarity to white-rot fungi than to litter decomposers, including 18 genes coding for unspecific peroxygenases and three dye-decolourising peroxidase genes expanding its lignocellulolytic machinery.
Conclusions: The genome resource will be useful for developing strategies towards genetic manipulation of A. aegerita, which will subsequently allow functional genetics approaches to elucidate fundamentals of fruiting and vegetative growth including lignocellulolysis.
Summary: Persistence with osteoporosis therapy is vital for fracture prevention. This non-interventional study of postmenopausal women receiving denosumab in Germany, Austria, Greece, and Belgium found that persistence with denosumab remains consistently high after 24 months in patients at high risk of fracture.
Purpose: Continued persistence with osteoporosis therapy is vital for fracture prevention. This non-interventional study of clinical practice evaluated medication-taking behavior of postmenopausal women receiving denosumab in Germany, Austria, Greece, and Belgium and factors influencing persistence.
Methods: Subcutaneous denosumab (60 mg every 6 months) was assigned according to prescribing information and local guidelines before and independently of enrollment; outcomes were recorded during routine practice for up to 24 months. Persistence was defined as receiving the subsequent injection within 6 months + 8 weeks of the previous injection and adherence as administration of subsequent injections within 6 months ± 4 weeks of the previous injection. Medication coverage ratio (MCR) was calculated as the proportion of time a patient was covered by denosumab. Associations between pre-specified baseline covariates and 24-month persistence were assessed using multivariable logistic regression.
Results: The 24-month analyses included 1479 women (mean age 66.3–72.5 years) from 140 sites; persistence with denosumab was 75.1–86.0%, adherence 62.9–70.1%, and mean MCR 87.4–92.4%. No covariate had a significant effect on persistence across all four countries. For three countries, a recent fall decreased persistence; patients were generally older with chronic medical conditions. In some countries, other covariates (e.g., older age, comorbidity, immobility, and prescribing reasons) decreased persistence. Adverse drug reactions were reported in 2.3–6.9% patients.
Conclusions: Twenty-four-month persistence with denosumab is consistently high among postmenopausal women in Europe and may be influenced by patient characteristics. Further studies are needed to identify determinants of low persistence.
Activation of Mitochondrial complex II-dependent respiration is beneficial for α-Synucleinopathies
(2015)
Parkinson’s disease and dementia with Lewy bodies are major challenges in research and clinical medicine world-wide and contribute to the most common neurodegenerative disorders. Previously, specific mitochondrial polymorphisms have been found to enhance clearance of amyloid-β from the brain of APP-transgenic mice leading to beneficial clinical outcome. It has been discussed whether specific mitochondrial alterations contribute to disease progression or even prevent toxic peptide deposition, as seen in many neurodegenerative diseases. Here, we investigated α-synuclein-transgenic C57BL/6J mice with the A30P mutation, and a novel A30P C57BL/6J mouse model with three mitochondrial DNA polymorphisms in the ND3, COX3 and mtRNAArg genes, as found in the inbred NOD/LtJ mouse strain. We were able to detect that the new model has increased mitochondrial complex II-respiration which occurs in parallel to neuronal loss and improved motor performance, although it exhibits higher amounts of high molecular weight species of α-synuclein. High molecular weight aggregates of different peptides are controversially discussed in the light of neurodegeneration. A favourable hypothesis states that high molecular weight species are protective and of minor importance for the pathogenesis of neurodegenerative disorders as compared to the extreme neurotoxic monomers and oligomers. Summarising, our results point to a potentially protective and beneficial effect of specific mitochondrial polymorphisms which cause improved mitochondrial complex II-respiration in α-synucleinopathies, an effect that could be exploited further for pharmaceutical interventions.
NMR spectroscopy is a powerful technique to study ribonucleic acids (RNAs) which are key players in a plethora of cellular processes. Although the NMR toolbox for structural studies of RNAs expanded during the last decades, they often remain challenging. Here, we show that solvent paramagnetic relaxation enhancements (sPRE) induced by the soluble, paramagnetic compound Gd(DTPA-BMA) provide a quantitative measure for RNA solvent accessibility and encode distance-to-surface information that correlates well with RNA structure and improves accuracy and convergence of RNA structure determination. Moreover, we show that sPRE data can be easily obtained for RNAs with any isotope labeling scheme and is advantageous regarding sample preparation, stability and recovery. sPRE data show a large dynamic range and reflect the global fold of the RNA suggesting that they are well suited to identify interaction surfaces, to score structural models and as restraints in RNA structure determination.
UICC classification accurately predicts overall survival but not recurrence-risk. We report here data of overall and first site-specific recurrence following curative surgery useful for the development of recurrence-oriented preventive target therapies. Patients who underwent resection for gastric cancer were stratified according to curability of surgery [curative (R0) vs non-curative resection], extent of surgery [limited (D1) vs extended (D2) node dissection] and pathological nodal/serosal status. The intent-to-treat principle, log-rank test and Cox regression analysis were used for statistical analysis of time-to-event (recurrence, death) endpoints. Curative resection only produced a chance of cure whereas survival was very poor following non-curative resection (P < 0.0001). For D2 R0 subgroup of patients, a pathological serosa and a node state-based classification into three groups, proved to be of clinical implication. Risk of recurrence after a median follow-up of 92 months was low among patients with both serosa and node-negative cancer (first group; 11%), moderate among those with either serosa or node-positive cancer (second group; 53%) and very high among those with both serosa and node-positive cancer (third group; 83%). In multivariate analysis, the relative risks of recurrence and death from gastric cancer among patients in the second and third groups, as compared to those in the first, were 7.07 (95% CI, 2.36–21.17; P = 0.0002) and 16.19 (95% CI, 5.76–45.54; P < 0.0001) respectively. First site-specific recurrence analysis revealed: low rate of loco-regional recurrence alone (12%), serosa state determinant factor of the site-recurrence (peritoneal for serosa-positive and haematogenous for serosa-negative cancers) and dramatic increase of all types of recurrence by the presence of nodal metastases. Our findings demonstrate that a pathological serosa- and node-based classification is very simple and predicts accurately site-specific recurrence-risks. Furthermore they reveal that risk of recurrence following curative D2 surgery alone is low for serosa- and node-negative cancers, but very high in serosa- and node-positive cancers suggesting the need for new therapeutic strategies in this subgroup of patients.
Background: Correct species identification of blow flies is a crucial step for understanding their biology, which can be used not only for designing fly control programs, but also to determine the minimum time since death. Identification techniques are usually based on morphological and molecular characters. However, the use of classical morphology requires experienced entomologists for correct identification; while molecular techniques rely on a sound laboratory expertise and remain ambiguous for certain taxa. Landmark-based geometric morphometric analysis of insect wings has been extensively applied in species identification. However, few wing morphometric analyses of blow fly species have been published.
Methods: We applied a landmark-based geometric morphometric analysis of wings for species identification of 12 medically and forensically important blow fly species of Thailand. Nineteen landmarks of each right wing of 372 specimens were digitised. Variation in wing size and wing shape was analysed and evaluated for allometric effects. The latter confirmed the influence of size on the shape differences between species and sexes. Wing shape variation among genera and species were analysed using canonical variates analysis followed by a cross-validation test.
Results: Wing size was not suitable for species discrimination, whereas wing shape can be a useful tool to separate taxa on both, genus and species level depending on the analysed taxa. It appeared to be highly reliable, especially for classifying Chrysomya species, but less robust for a species discrimination in the genera Lucilia and Hemipyrellia. Allometry did not affect species separation but had an impact on sexual shape dimorphism.
Conclusions: A landmark-based geometric morphometric analysis of wings is a useful additional method for species discrimination. It is a simple, reliable and inexpensive method, but it can be time-consuming locating the landmarks for a large scale study and requires non-damaged wings for analysis.
The radiative capture cross section of 238U is very important for the developing of new reactor technologies and the safety of existing ones. Here the preliminary results of the 238U(n,γ) cross section measurement performed at n_TOF with C6D6 scintillation detectors are presented, paying particular attention to data reduction and background subtraction.
Background: Von Willebrand disease (VWD) is the most common inherent bleeding disorder. Gingival bleeding is a frequently reported symptom of VWD. However, gingival bleeding is also a leading symptom of plaque-induced gingivitis and untreated periodontal disease. In type 1 VWD gingival bleeding was not increased compared to controls. Thus, this study evaluated whether type 2 and 3 VWD determines an increased susceptibility to gingival bleeding in response to the oral biofilm.
Methods: Twenty-four cases and 24 controls matched for age, sex, periodontal diagnosis, number of teeth and smoking were examined hematologically (VWF antigen, VWF activity, factor VIII activity) and periodontally (Gingival Bleeding Index [GBI]), bleeding on probing [BOP], Plaque Control Record [PCR], periodontal inflamed surface area [PISA], vertical probing attachment level).
Results: BOP (VWD: 14.5±10.1%; controls: 12.3±5.3%; p = 0.542) and GBI (VWD: 10.5±9.9%; controls: 8.8±4.8%; p = 0.852) were similar for VWD and controls. Multiple regressions identified female sex, HbA1c, PCR and PISA to be associated with BOP. HbA1c and PCR were associated with GBI. Number of remaining teeth was negatively correlated with BOP and GBI.
Conclusion: Type 2 and 3 VWD are not associated with a more pronounced inflammatory response to the oral biofilm in terms of BOP and GBI.
Stimulation of renal collecting duct principal cells with antidiuretic hormone (arginine-vasopressin, AVP) results in inhibition of the small GTPase RhoA and the enrichment of the water channel aquaporin-2 (AQP2) in the plasma membrane. The membrane insertion facilitates water reabsorption from primary urine and fine-tuning of body water homeostasis. Rho guanine nucleotide exchange factors (GEFs) interact with RhoA, catalyze the exchange of GDP for GTP and thereby activate the GTPase. However, GEFs involved in the control of AQP2 in renal principal cells are unknown. The A-kinase anchoring protein, AKAP-Lbc, possesses GEF activity, specifically activates RhoA, and is expressed in primary renal inner medullary collecting duct principal (IMCD) cells. Through screening of 18,431 small molecules and synthesis of a focused library around one of the hits, we identified an inhibitor of the interaction of AKAP-Lbc and RhoA. This molecule, Scaff10-8, bound to RhoA, inhibited the AKAP-Lbc-mediated RhoA activation but did not interfere with RhoA activation through other GEFs or activities of other members of the Rho family of small GTPases, Rac1 and Cdc42. Scaff10-8 promoted the redistribution of AQP2 from intracellular vesicles to the periphery of IMCD cells. Thus, our data demonstrate an involvement of AKAP-Lbc-mediated RhoA activation in the control of AQP2 trafficking.
Background: Published estimates of mortality and progression to AIDS as children with HIV approach adulthood are limited. We describe rates and risk factors for death and AIDS-defining events in children and adolescents after initiation of combination antiretroviral therapy (cART) in 17 middle- and high-income countries, including some in Western and Central Europe (W&CE), Eastern Europe (Russia and Ukraine), and Thailand.
Methods and findings: Children with perinatal HIV aged <18 years initiating cART were followed until their 21st birthday, transfer to adult care, death, loss to follow-up, or last visit up until 31 December 2013. Rates of death and first AIDS-defining events were calculated. Baseline and time-updated risk factors for early/late (≤/>6 months of cART) death and progression to AIDS were assessed. Of 3,526 children included, 32% were from the United Kingdom or Ireland, 30% from elsewhere in W&CE, 18% from Russia or Ukraine, and 20% from Thailand. At cART initiation, median age was 5.2 (IQR 1.4–9.3) years; 35% of children aged <5 years had a CD4 lymphocyte percentage <15% in 1997–2003, which fell to 15% of children in 2011 onwards (p < 0.001). Similarly, 53% and 18% of children ≥5 years had a CD4 count <200 cells/mm3 in 1997–2003 and in 2011 onwards, respectively (p < 0.001). Median follow-up was 5.6 (2.9–8.7) years. Of 94 deaths and 237 first AIDS-defining events, 43 (46%) and 100 (42%) were within 6 months of initiating cART, respectively. Multivariable predictors of early death were: being in the first year of life; residence in Russia, Ukraine, or Thailand; AIDS at cART start; initiating cART on a nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimen; severe immune suppression; and low BMI-for-age z-score. Current severe immune suppression, low current BMI-for-age z-score, and current viral load >400 c/mL predicted late death. Predictors of early and late progression to AIDS were similar. Study limitations include incomplete recording of US Centers for Disease Control (CDC) disease stage B events and serious adverse events in some countries; events that were distributed over a long time period, and that we lacked power to analyse trends in patterns and causes of death over time.
Conclusions: In our study, 3,526 children and adolescents with perinatal HIV infection initiated antiretroviral therapy (ART) in countries in Europe and Thailand. We observed that over 40% of deaths occurred ≤6 months after cART initiation. Greater early mortality risk in infants, as compared to older children, and in Russia, Ukraine, or Thailand as compared to W&CE, raises concern. Current severe immune suppression, being underweight, and unsuppressed viral load were associated with a higher risk of death at >6 months after initiation of cART.
In optogenetics, rhodopsins were established as light-driven tools to manipulate neuronal activity. However, during long-term photostimulation using channelrhodopsin (ChR), desensitization can reduce effects. Furthermore, requirement for continuous presence of the chromophore all-trans retinal (ATR) in model systems lacking sufficient endogenous concentrations limits its applicability. We tested known, and engineered and characterized new variants of de- and hyperpolarizing rhodopsins in Caenorhabditis elegans. ChR2 variants combined previously described point mutations that may synergize to enable prolonged stimulation. Following brief light pulses ChR2(C128S;H134R) induced muscle activation for minutes or even for hours (‘Quint’: ChR2(C128S;L132C;H134R;D156A;T159C)), thus featuring longer open state lifetime than previously described variants. Furthermore, stability after ATR removal was increased compared to the step-function opsin ChR2(C128S). The double mutants C128S;H134R and H134R;D156C enabled increased effects during repetitive stimulation. We also tested new hyperpolarizers (ACR1, ACR2, ACR1(C102A), ZipACR). Particularly ACR1 and ACR2 showed strong effects in behavioral assays and very large currents with fast kinetics. In sum, we introduce highly light-sensitive optogenetic tools, bypassing previous shortcomings, and thus constituting new tools that feature high effectiveness and fast kinetics, allowing better repetitive stimulation or investigating prolonged neuronal activity states in C. elegans and, possibly, other systems.
The increased susceptibility to infections of neonates is caused by an immaturity of the immune system as a result of both qualitative and quantitative differences between neonatal and adult immune cells. With respect to B cells, neonatal antibody responses are known to be decreased. Accountable for this is an altered composition of the neonatal B cell compartment towards more immature B cells. However, it remains unclear whether the functionality of individual neonatal B cell subsets is altered as well. In the current study we therefore compared phenotypical and functional characteristics of corresponding neonatal and adult B cell subpopulations. No phenotypic differences could be identified with the exception of higher IgM expression in neonatal B cells. Functional analysis revealed differences in proliferation, survival, and B cell receptor signaling. Most importantly, neonatal B cells showed severely impaired class-switch recombination (CSR) to IgG and IgA. This was associated with increased expression of miR-181b in neonatal B cells. Deficiency of miR-181b resulted in increased CSR. With this, our results highlight intrinsic differences that contribute to weaker B cell antibody responses in newborns.
Aim: To study the transepithelial transport characteristics of the polyamine putrescine in human intestinal Caco-2 cell monolayers to elucidate the mechanisms of the putrescine intestinal absorption.
Methods: The transepithelial transport and the cellular accumulation of putrescine was measured using Caco-2 cell monolayers grown on permeable filters.
Results: Transepithelial transport of putrescine in physiological concentrations ( > 0.5 mM) from the apical to basolateral side was linear. Intracellular accumulation of putrescine was higher in confluent than in fully differentiated Caco-2 cells, but still negligible (less than 0.5%) of the overall transport across the monolayers in apical to basolateral direction.EGF enhanced putrescine accumulation in Caco-2 cells by four fold, as well as putrescine conversion to spermidine and spermine by enhancing the activity of S adenosylmethionine decarboxylase. However, EGF did not have any significant influence on putrescine flux across the Caco- 2 cell monolayers. Excretion of putrescine from Caco-2 cells into the basolateral medium did not exceed 50 picomoles, while putrescine passive flux from the apical to the basolateral chamber, contributed hundreds of micromoles polyamines to the basolateral chamber.
Conclusion: Transepithelial transport of putrescine across Caco-2 cell monolayers occurs in passive diffusion, and is not influenced when epithelial cells are stimulated to proliferate by a potent mitogen such as EGF.
To analyze prospectively the interventional and clinical aspects of computed tomography-guided direct intratumoural injection of a novel chemotherapeutic administration and the parenchymal changes of tumour and necrosis in malignant liver tumours. Eight patients with 17 colorectal liver metastases were treated with a mean of 5.1 injections and nine patients with 13 hepatocellular carcinoma nodules with a mean of 3.1 treatments with computed tomography guided local applications of a novel cisplatin/epinephrine gel. This application provides a higher local and lower systemic drug concentration. Volumes of tumour and necrosis prior and after treatment were measured by computer generated volumetric analysis. Contrast enhanced studies verified pretherapeutic viable tumour volumes with a value of 77.4 ml in the metastases and 29.2 ml in the hepatocellular carcinoma nodules. Intratumoural drug application resulted in a significant increase of necrosis and a decrease in viable tumour volume to be 68.3 ml in metastases and 14.5 ml in hepatocellular carcinoma. Local therapy control rate for the follow up to 6 months was 38 and 71% for the group of metastases and hepatocellular carcinoma, respectively. Direct intratumoural injection of cisplatin/epinepthrine injectable gel is a feasible and good tolerated method and results in the development of a statistically significant increase in necrosis in malignant liver tumours. For hepatocellular carcinoma a higher local therapy control rate compared to colorectal metastases can be reported.
The proliferative stimulus of the epidermal growth factor (EGF) in human epithelial cells is mediated by its binding to the external domain of the EGF receptor (EGF-R). The purpose of this study was to investigate whether growth arrest of tumors treated with anti-EGFR MAb (EMD 55900) was dependent on EGF-R expression and distinct histopathologic criteria of those neoplasms. Nine different adenocarcinomas, squamous cell carcinomas and two neoplastic epithelial cell lines (A431 and Detroit 562), which were characterized by high EGF-R expression, were xenotransplanted onto NMRI-nu/nu mice and treated with an anti-EGF-R antibody (EMD 55900). Results revealed that EGF-R expression and distinct histopathologic growth patterns play an important role for the therapeutic effect of the EGF-R antibody treatment. Tumors with high epithelial cellularity and little connective tissue responded to EMD 55900 treatment to a greater degree of growth reduction than tumors with lower cellularity. These results will be helpful for evaluation of patients who would benefit from tumor therapy with anti-EGF-R antibody.
We generated transgenic tomato plants with altered expression of heat stress transcription factor HsfA1. Plants with 10-fold overexpression of HsfA1 (OE plants) were characterized by a singleHsfA1 transgene cassette, whereas plants harboring a tandem inverted repeat of the cassette showed cosuppression (CS plants) by posttranscriptional silencing of the HsfA1 gene connected with formation of small interfering RNAs. Under normal growth conditions, major developmental parameters were similar for wild-type (WT), OE, and CS plants. However, CS plants and fruits were extremely sensitive to elevated temperatures, because heat stress-induced synthesis of chaperones and Hsfs was strongly reduced or lacking. Despite the complexity of the plant Hsf family with at least 17 members in tomato, HsfA1 has a unique function as master regulator for induced thermotolerance. Using transient reporter assays with mesophyll protoplasts from WT tomato, we demonstrated that plasmid-encoded HsfA1 and HsfA2 were well expressed. However, in CS protoplasts the cosuppression phenomenon was faithfully reproduced. Only transformation with HsfA2 expression plasmid led to normal expression of the transcription factor and reporter gene activation, whereas even high amounts of HsfA1 expression plasmids were silenced. Thermotolerance in CS protoplasts was restored by plasmid-borne HsfA2, resulting in expression of chaperones, thermoprotection of firefly luciferase, and assembly of heat stress granules.
Background: Leaf venation traits are important for many research fields such as systematics and evolutionary biology, plant physiology, climate change, and paleoecology. In spite of an increasing demand for vein trait data, studies are often still data-limited because the development of methods that allow rapid generation of large sets of vein data has lagged behind. Recently, non-destructive X-ray technology has proven useful as an alternative to traditional slow and destructive chemical-based methods. Non-destructive techniques more readily allow the use of herbarium specimens, which provide an invaluable but underexploited resource of vein data and related environmental information. The utility of 2D X-ray technology and microfocus X-ray computed tomography, however, has been compromised by insufficient image resolution. Here, we advanced X-ray technology by increasing image resolution and throughput without the application of contrast agents.
Results: For 2D contact microradiography, we developed a method which allowed us to achieve image resolutions of up to 7 µm, i.e. a 3.6-fold increase compared to the industrial standard (25 µm resolution). Vein tracing was further optimized with our image processing standards that were specifically adjusted for different types of leaf structure and the needs of higher imaging throughput. Based on a test dataset, in 91% of the samples the 7 µm approach led to a significant improvement in estimations of minor vein density compared to the industrial standard. Using microfocus X-ray computed tomography, very high-resolution images were obtained from a virtual 3D–2D transformation process, which was superior to that of 3D images.
Conclusions: Our 2D X-ray method with a significantly improved resolution advances rapid non-destructive bulk scanning at a quality that in many cases is sufficient to determine key venation traits. Together with our high-resolution microfocus X-ray computed tomography method, both non-destructive approaches will help in vein trait data mining from museum collections, which provide an underexploited resource of historical and recent data on environmental and evolutionary change. In spite of the significant increase in effective image resolution, a combination of high-throughput and full visibility of the vein network (including the smallest veins and their connectivity) remains challenging, however.
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.
Im Rahmen der forstlichen Standortserkundung werden Informationen über die für das Waldwachstum wichtigen Faktoren Lage, Klima und Boden erhoben. Diese Daten bilden die Grundlage für die Beurteilung eines Standortes hinsichtlich seiner Baumarteneignung, seines Leistungsvermögens und möglicher Produktionsrisiken. Die forstliche Standortskartierung ist föderal organisiert, sodass sich historisch länderspezifische Kartierverfahren entwickelt haben (Gauer 2009). Mit Ausnahme der ostdeutschen Bundesländer, in denen die Kartierung auf einer gemeinsamen Standortserkundungsanleitung basiert (Veb Forstprojektierung Potsdam 1974), existieren nur länderweise gültige Kartenwerke.
Die steigende Nachfrage nach großmaßstäblichen Standorts-und Bodeninformationen im Bereich der forstlichen Planungs- und Entscheidungsunterstützung umfasst auch die Grundwasserflurabstände. Diese gehen entweder direkt in statistische und prozessorientierte Modelle ein oder sind eine wichtige Grundlage für die digitale Standortsprognose. In dieser Untersuchung wurde für das niedersächsische Tiefland ein Disaggregierungsansatz entwickelt, mit dem der mittlere Grundwassertiefstand (MNGW) der flächendeckenden BÜK50 von Niedersachsen (1 : 50000) in die Grundwasserflurabstandseinstufung der Standortskartierung (1 : 25000) übersetzt werden kann, die nicht flächendeckend vorliegt. Die Ergebnisse zeigen, dass durch die Disaggregierung eine Verbesserung der Ableitung von Grundwasserinformation für Waldstandorte aus der BÜK50 erreicht werden kann. Die Genauigkeit (AC) erhöhte sich von 0,64 auf 0,69 und der Kappa-Koeffizient von 0,34 auf 0,48. Trotzdem ist die Übereinstimmung zwischen modellierten und kartierten Einstufungen mit einem Kappa-Koeffizienten von 0,48 des Validierungsdatensatzes nur als „moderat“ zu bezeichnen.
Seit den 1980er Jahren wird in Baden-Württemberg die Bodenschutzkalkung angewendet, um Säureeinträge aus der Luft zu kompensieren. Die vorliegende Arbeit ist eine Auswertung der Kalkungsdokumentation aus Daten der Unteren Forstbehörden in Baden-Württemberg, die 2005 erstmalig von der FVA zusammengeführt wurde. Es wird dargestellt, dass der Fokus der Kalkungen bisher deutlich auf den Waldflächen des Schwarzwaldes lag, die durch die Grundgesteine des Buntsandsteins und des kristallinen Grundgebirges natürlicherweise und auch immissionsbedingt zu starken Bodenversauerungen neigen. Aber auch im Keuperbergland, dem Odenwald und im Verbreitungsgebiet der Altmoräne in Oberschwaben sind seit den 1980er Jahren regelmäßig Kalkungen durchgeführt worden. Die lehmigen Böden der Nördlichen Altmoräne wurden insbesondere seit 2005 deutlich mehr gekalkt, was die Veränderung der Kalkungsausrichtung hin zu den produktiveren, lehmigen Standorten zeigt. Die Auswertung der Kalkungsdokumentation geht auf verwendete Ausbringungsmaterialien und -techniken ein und stellt die unterschiedliche Flächenbedeutung der Waldkalkung für die zwei Schwerpunkt-Regionen Nordschwarzwald und Nördliche Altmoräne dar. Die Kalkungsdokumentation beruht auf analogen Karteneinträgen der Forstämter, welche die gekalkten Waldstandorte auf Ebene der Distrikte und Waldabteilungen abbilden, aber nicht detailscharf auf die Aussparung kalkungssensitiver Biotope eingehen.
Hartholzauwälder gehören mit bis zu acht Baumarten in der Kronenschicht zu den Wäldern mit der höchsten Baumartenvielfalt in Europa und beherbergen eine Vielzahl gefährdeter Pflanzen- und Tierarten. Das Fehlen von Eichen in der Etablierungsphase in ansonsten eichenreichen Waldgesellschaften wie Hartholzauen ist daher naturschutzfachlich gravierend. Vielerorts wird mit starken waldbaulichen Eingriffen und finanziellem Aufwand versucht, zumindest einen Anteil an Stieleiche in die nächste Bestandesgeneration hinüber zu retten. Hinzu kommt die eher konzeptionelle Frage der Natürlichkeit der Stieleiche in Hartholzauwäldern. In der Hartholzaue im Naturschutzgebiet Kühkopf-Knoblochsaue in Hessen wurde Stieleichenverjüngung in der Etablierungsphase auf zwei unterschiedlichen ungesteuerten Sukzessionsflächen untersucht, welche nach starken Hochwässern entstanden und von Hochwasser geprägt sind. Dies beinhaltet die Beschreibung des Standorts, die Quantifizierung der Eichenanteile, die Einschätzung ihrer Vitalität sowie die Charakterisierung des Wuchses der Stieleiche. Auf der insgesamt 4,53 Hektar großen Inventurfläche fanden sich fünf Strukturtypen (Straten) in Form (1) eines strauchreichen Pionierwalds; (2) eines offenen bis lückigen Gehölzkomplexes; (3) eines halboffenen bis geschlossenen Gehölzkomplexes; (4) eines fast geschlossenen Gebüschkomplexes, gezäunt; sowie (5) eines geschlossenen Pionierwalds, gezäunt. Auf diesen kamen insgesamt 155 Stieleichen vor und wurden aufgenommen (34 Stieleichen/ha). Es zeigte sich, dass Wildverbiss die Etablierung der Eiche zwar behinderte, dennoch in allen Straten stabile, vitale Jungeichen heranwachsen konnten. Starke Überschirmung und Konkurrenz durch Bodenvegetation wirkten sich negativ auf das Wachstum aus, bis hin zum Ausfall von Eichenverjüngung in Herden von Goldrute (Solidago canadensis) und Reitgras (Calamagrostis epigeios). Die Bestände am Kühkopf zeigen, dass sich die Stieleiche nach starken Hochwasserereignissen auf neu aufgelandetem Substrat unter den dann konkurrenzarmen Bedingungen und bei zugleich kontrolliertem Wildstand in Hartholzauen erfolgreich natürlich etabliert und auch in die Baumschicht einwächst, also Bestandteil der natürlichen Vegetation dieses Lebensraumes ist. Das Ausbleiben der natürlichen Eichenetablierung in den heutigen Überflutungsauen ist demnach auf die dort weitgehend fehlende Substratdynamik nach starken Hochwässern und damit fehlende natürliche Auensukzession sowie hohe Rehwilddichten zurückzuführen.
Bilberry (Vaccinium myrtillus L.) is a dwarf shrub with high ecological relevance as habitat and as a food source for many animals in mountain forests of central Europe. This species benefits from conifer forests and declines with an increase of broadleaved tree species in the canopy. The ongoing large-scale conversion from conifer to broadleaved forests may significantly alter the ground vegetation, especially the dominance of a key species such as bilberry. We used morphological indicators to investigate the vitality of bilberry. The first objective was to determine whether the vitality of bilberry is negatively impacted by increasing the proportion of beech (Fagus sylvatica L.) in Norway spruce (Picea abies Karst.) forests. The vitality of bilberry was measured by its cover, height, biomass, shoot length and basal diameter. The second objective was to determine whether these changes in bilberry vitality were related to light, canopy cover, soil pH, organic layer mass and tree species. The data was collected from three study areas in the southern and central Black Forest. The bedrock consisted of gneiss and granite whereas the stands were either: pure beech, a mixture of beech and spruce or pure spruce. The stands were located adjacent to each other. On all three areas a higher vitality of bilberry was observed under spruce compared to beech. Mixed effect models show that the occurrence of spruce is the most important variable explaining the increase in bilberry biomass. Light had a small positive effect, whereas soil properties had negligible effects and were site specific. These results are a strong indication of the negative influence that beech has on bilberry in conifer dominated forests. This has to be taken into consideration when developing silvicultural approaches and should be a consideration when making plans for the preservation of habitat for species like capercaillie (Tetrao urogallus L.). This is even more important today because the recent trend in central European forestry is to increase the proportion of beech.
Im November 2015 wurde in Jena das Buch „Die Botaniker Thüringens“ als 18. Beiheft der Schriftenreihe Haussknechtia der Thüringischen Botanischen Gesellschaft e. V. vorgestellt. Es ist die erste Auflistung aller Thüringer Botaniker überhaupt und ergänzt bzw. erweitert das Wissen über bereits zahlreiche in der „Flora von Thüringen“ (Zündorf & al. 2006) erwähnte Botaniker.
Bioindicators are organisms able to provide indirectly or directly information on the impact of pollutants in the environment. The content of heavy metals or other toxic compounds in these living organisms is of great interest to assess the level of contaminants. Leaves of the most common deciduous trees (Acer pseudoplatanus L., Betula pendula Roth, Carpinus betulus L., Cercis siliquastrum L., Ginkgo biloba L., Liquidambar styraciflua, Quercus robur L. and Tilia cordata Miller) and two invasive tree species Ailanthus altissima P. Mill. and Robinia pseudoacacia L., in the City of Bolzano (southern Alps in Northern Italy), were therefore studied to assess their suitability as bioindicators for the trace elements Cd, Cu, Mn, Pb, and Zn, mainly considered as traffic related elements. Leaves and soil samples were investigated, both from high-density traffic roads and control sites of minor traffic impact, such as parks. Our data reveal that Betula pendula has a considerable Zn accumulation potential compared to the other investigated tree species. The maximum value measured for Zn in a Betula specimen is 200 mg kg-1 dry weight. With regard to the soils, considering the geoaccumulation index, most of the analyzed soils belong to the first class, i. e. uncontaminated (Igeo ≤ 0) for all analyzed elements. Moreover, in several samples collected in high traffic areas, Cu and Zn show values within 1 < Igeo ≤ 2 (moderately contaminated). This allows to hypothesize a traffic-related origin for these elements. For this reason, B. pendula can be considered a potential heavy metal accumulator and therefore a good bioindicator for these urban pollutants. Since B. pendula is widely distributed in urban areas in Central and Northern Europe, it can be considered a species suitable for a systematic and comparative monitoring network.
Auf der Grundlage eines neuen Forschungskonzeptes für die Dauerbeobachtung in 26 bayerischen Naturwaldreservaten wurde in vier gemischten, laubbaumdominierten Reservaten mit der Aufnahme von Waldstrukturdaten und waldökologisch besonders wichtigen Artengruppen begonnen. Die dabei gewonnenen Artdaten zur Bodenvegetation, xylobionten Käfern, Schnecken und Pilzen wurden mit den Strukturdaten des Waldbestandes auf Probekreisebene verschnitten. Alle Artengruppen zeigten ähnliche Muster hinsichtlich ihrer Artenzusammensetzung in Beziehung zu Strukturparametern wie dem Buchenanteil des Bestandes und in zweiter Ebene zu Beteiligung der Hainbuche. Zudem konnten Vögel auf der Basis von Rasterkartierungen über die gesamten Reservatsflächen erfasst werden. Es kann daher abgeleitet werden, dass auch Aufnahmen im Rahmen eines entsprechend einfachen Monitorings Beziehungen zwischen den Arten und Waldstrukturen aufzeigen können. Genauere waldökologische Beziehungen zu naturschutzfachlich interessanten Arten wie Naturnähezeigern und Urwaldreliktarten lassen sich mit den Monitoringansätzen jedoch kaum ableiten.
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a condition of abnormal heart rhythm (arrhythmia), induced by physical activity or stress. Mutations in ryanodine receptor 2 (RyR2), a Ca2+ release channel located in the sarcoplasmic reticulum (SR), or calsequestrin 2 (CASQ2), a SR Ca2+ binding protein, are linked to CPVT. For specific drug development and to study distinct arrhythmias, simple models are required to implement and analyze such mutations. Here, we introduced CPVT inducing mutations into the pharynx of Caenorhabditis elegans, which we previously established as an optogenetically paced heart model. By electrophysiology and video-microscopy, we characterized mutations in csq-1 (CASQ2 homologue) and unc-68 (RyR2 homologue). csq-1 deletion impaired pharynx function and caused missed pumps during 3.7 Hz pacing. Deletion mutants of unc-68, and in particular the point mutant UNC-68(R4743C), analogous to the established human CPVT mutant RyR2(R4497C), were unable to follow 3.7 Hz pacing, with progressive defects during long stimulus trains. The pharynx either locked in pumping at half the pacing frequency or stopped pumping altogether, possibly due to UNC-68 leakiness and/or malfunctional SR Ca2+ homeostasis. Last, we could reverse this ‘worm arrhythmia’ by the benzothiazepine S107, establishing the nematode pharynx for studying specific CPVT mutations and for drug screening.
Background: Malaria remains one of the most serious infections for travellers to tropical countries. Due to the lack of harmonized guidelines a large variety of treatment regimens is used in Europe to treat severe malaria.
Methods: The European Network for Tropical Medicine and Travel Health (TropNet) conducted an 8-year, multicentre, observational study to analyse epidemiology, treatment practices and outcomes of severe malaria in its member sites across Europe. Physicians at participating TropNet centres were asked to report pseudonymized retrospective data from all patients treated at their centre for microscopically confirmed severe Plasmodium falciparum malaria according to the 2006 WHO criteria.
Results: From 2006 to 2014 a total of 185 patients with severe malaria treated in 12 European countries were included. Three patients died, resulting in a 28-day survival rate of 98.4%. The majority of infections were acquired in West Africa (109/185, 59%). The proportion of patients treated with intravenous artesunate increased from 27% in 2006 to 60% in 2013. Altogether, 56 different combinations of intravenous and oral drugs were used across 28 study centres. The risk of acute renal failure (36 vs 17% p = 0.04) or cerebral malaria (54 vs 20%, p = 0.001) was significantly higher in patients ≥60 years than in younger patients. Respiratory distress with the need for mechanical ventilation was significantly associated with the risk of death in the study population (13 vs 0%, p = 0.001). Post-artemisinin delayed haemolysis was reported in 19/70 (27%) patients treated with intravenous artesunate.
Conclusion: The majority of patients with severe malaria in this study were tourists or migrants acquiring the infection in West Africa. Intravenous artesunate is increasingly used for treatment of severe malaria in many European treatment centres and can be given safely to European patients with severe malaria. Patients treated with intravenous artesunate should be followed up to detect and manage late haemolytic events.
This study investigated associations between parenting stress in parents and self-reported stress in children with children's diurnal cortisol secretion and whether these associations are moderated by known stress-regulating capacities, namely child cognitive control. Salivary cortisol concentrations were assessed from awakening to evening on two weekend days from 53 6-to-7-year-old children. Children completed a cognitive control task and a self-report stress questionnaire with an experimenter, while parents completed a parenting stress inventory. Hierarchical, linear mixed effects models revealed that higher parenting stress was associated with overall reduced cortisol secretion in children, and this effect was moderated by cognitive control. Specifically, parenting stress was associated with reduced diurnal cortisol levels in children with lower cognitive control ability and not in children with higher cognitive control ability. There were no effects of self-reported stress in children on their cortisol secretion, presumably because 6-to-7-year-old children cannot yet self-report on stress experiences. Our results suggest that higher cognitive control skills may buffer the effects of parenting stress in parents on their children’s stress regulation in middle childhood. This could indicate that training cognitive control skills in early life could be a target to prevent stress-related disorders.
Progressive neurodegenerative diseases plague millions of individuals both in the United States and across the world. The current pathology of progressive neurodegenerative tauopathies, such as Alzheimer’s disease (AD), Pick’s disease, frontotemporal dementia (FTD), and progressive supranuclear palsy, primarily revolves around phosphorylation and hyperphosphorylation of the tau protein. However, more recent evidence suggests acetylation of tau protein at lysine 280 may be a critical step in molecular pathology of these neurodegenerative diseases prior to the tau hyperphosphorylation. Secondary injury cascades such as oxidative stress, endoplasmic reticulum stress, and neuroinflammation contribute to lasting damage within the brain and can be induced by a number of different risk factors. These injury cascades funnel into a common pathway of early tau acetylation, which may serve as the catalyst for progressive degeneration. The post translational modification of tau can result in production of toxic oligomers, contributing to reduced solubility as well as aggregation and formation of neurofibrillary tangles, the hallmark of AD pathology. Chronic Traumatic Encephalopathy (CTE), caused by repetitive brain trauma is also associated with a hyperphosphorylation of tau. We postulated acetylation of tau at lysine 280 in CTE disease could be present prior to the hyperphosphorylation and tested this hypothesis in CTE pathologic specimens. We also tested for ac-tau 280 in early stage Alzheimer’s disease (Braak stage 1). Histopathological examination using the ac tau 280 antibody was performed in three Alzheimer's cases and three CTE patients. Presence of ac-tau 280 was confirmed in all cases at early sites of disease manifestation. These findings suggest that tau acetylation may precede tau phosphorylation and could be the first "triggering" event leading to neuronal loss. To the best of our knowledge, this is the first study to identify acetylation of the tau protein in CTE. Prevention of tau acetylation could possibly serve as a novel target for stopping neurodegeneration before it fully begins. In this study, we highlight what is known about tau acetylation and neurodegeneration.
Online reading behavior can be regarded as a "new" form of cultural capital in today’s digital world. However, it is unclear whether "traditional" mechanisms of cultural and social reproduction are also found in this domain, and whether they manifest uniformly across countries at different stages of development. This article analyzes whether the early home literacy environment has an impact on informational online reading behavior among adolescents and whether this association varies between countries with different levels of digitalization and educational expansion. Data from the 2009 Programme for International Student Assessment (PISA) were used for the empirical analyses. The results of regression models with country-fixed effects indicate a positive association between literacy activities in early childhood and informational online reading at age 15. This association was quite stable across countries. These findings are discussed in light of cultural and social reproduction theory and digital divide research.
The toolbox for imaging molecules is well-equipped today. Some techniques visualize the geometrical structure, others the electron density or electron orbitals. Molecules are many-body systems for which the correlation between the constituents is decisive and the spatial and the momentum distribution of one electron depends on those of the other electrons and the nuclei. Such correlations have escaped direct observation by imaging techniques so far. Here, we implement an imaging scheme which visualizes correlations between electrons by coincident detection of the reaction fragments after high energy photofragmentation. With this technique, we examine the H2 two-electron wave function in which electron–electron correlation beyond the mean-field level is prominent. We visualize the dependence of the wave function on the internuclear distance. High energy photoelectrons are shown to be a powerful tool for molecular imaging. Our study paves the way for future time resolved correlation imaging at FELs and laser based X-ray sources.
Secretins form multimeric channels across the outer membrane of Gram-negative bacteria that mediate the import or export of substrates and/or extrusion of type IV pili. The secretin complex of Thermus thermophilus is an oligomer of the 757-residue PilQ protein, essential for DNA uptake and pilus extrusion. Here, we present the cryo-EM structure of this bifunctional complex at a resolution of ~7 Å using a new reconstruction protocol. Thirteen protomers form a large periplasmic domain of six stacked rings and a secretin domain in the outer membrane. A homology model of the PilQ protein was fitted into the cryo-EM map. A crown-like structure outside the outer membrane capping the secretin was found not to be part of PilQ. Mutations in the secretin domain disrupted the crown and abolished DNA uptake, suggesting a central role of the crown in natural transformation.
Infections of the central nervous system (CNS) are infrequently diagnosed in immunocompetent patients, but they do occur in a significant proportion of patients with hematological disorders. In particular, patients undergoing allogeneic hematopoietic stem-cell transplantation carry a high risk for CNS infections of up to 15%. Fungi and Toxoplasma gondii are the predominant causative agents. The diagnosis of CNS infections is based on neuroimaging, cerebrospinal fluid examination and biopsy of suspicious lesions in selected patients. However, identification of CNS infections in immunocompromised patients could represent a major challenge since metabolic disturbances, side-effects of antineoplastic or immunosuppressive drugs and CNS involvement of the underlying hematological disorder may mimic symptoms of a CNS infection. The prognosis of CNS infections is generally poor in these patients, albeit the introduction of novel substances (e.g. voriconazole) has improved the outcome in distinct patient subgroups. This guideline has been developed by the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO) with the contribution of a panel of 14 experts certified in internal medicine, hematology/oncology, infectious diseases, intensive care, neurology and neuroradiology. Grades of recommendation and levels of evidence were categorized by using novel criteria, as recently published by the European Society of Clinical Microbiology and Infectious Diseases.
Patients who undergo endovascular repair of aortic aneurysms (EVAR) require life-long surveillance because complications including, in particular, endoleaks, aneurysm rupture, and graft dislocation are diagnosed in a certain share of the patient population and may occur at any time after the original procedure. Radiation exposure in patients undergoing EVAR and post-EVAR surveillance has been investigated by previous authors. Arriving at realistic exposure data is essential because radiation doses resulting from CT were shown to be not irrelevant. Efforts directed at identification of factors impacting the level of radiation exposure in both the course of the EVAR procedure and post-EVAR endovascular interventions and CTAs are warranted as potentially modifiable factors may offer opportunities to reduce the radiation. In the light of the risks found to be associated with radiation exposure and considering the findings above, those involved in EVAR and post-EVAR surveillance should aim at optimal dose management.
IKZF1 deletion (ΔIKZF1) is an important predictor of relapse in childhood B-cell precursor acute lymphoblastic leukemia. Because of its clinical importance, we previously mapped breakpoints of intragenic deletions and developed a multiplex PCR assay to detect recurrent intragenic ΔIKZF1. Since the multiplex PCR was not able to detect complete deletions (IKZF1 Δ1-8), which account for ~30% of all ΔIKZF1, we aimed at investigating the genomic scenery of IKZF1 Δ1-8. Six samples of cases with IKZF1 Δ1-8 were analyzed by microarray assay, which identified monosomy 7, isochromosome 7q, and large interstitial deletions presenting breakpoints within COBL gene. Then, we established a multiplex ligation-probe amplification (MLPA) assay and screened copy number alterations within chromosome 7 in 43 diagnostic samples with IKZF1 Δ1-8. Our results revealed that monosomy and large interstitial deletions within chromosome 7 are the main causes of IKZF1 Δ1-8. Detailed analysis using long distance inverse PCR showed that six patients (16%) had large interstitial deletions starting within intronic regions of COBL at diagnosis, which is ~611 Kb downstream of IKZF1, suggesting that COBL is a hotspot for ΔIKZF1. We also investigated a series of 25 intragenic deletions (Δ2–8, Δ3–8 or Δ4–8) and 24 relapsed samples, and found one IKZF1-COBL tail-to-tail fusion, thus supporting that COBL is a novel hotspot for ΔIKZF1. Finally, using RIC score methodology, we show that breakpoint sequences of IKZF1 Δ1-8 are not analog to RAG-recognition sites, suggesting a different mechanism of error promotion than that suggested for intragenic ΔIKZF1.
In der Arbeit wird dargestellt, wie bzw. inwieweit Zuweisungen der Stamm-Nährkraft zu konkreten anhydromorphen Bodenprofilen innerhalb des SEA95-Systems auch auf Basis der Merkmale einzelner Bodenlagen (Horizonte i. w. S.) vorgenommen werden können, um einen Übergang von rein bodenklassenbasierter Zuweisung (über Feinbodenformen) zu einem weitgehend quantifizierenden Verfahren zu ermöglichen. Die benötigten Bodenlagenmerkmale sind Tiefe, Körnung, KMgCaP-Serie (Lithochemie) des Substrates, Humosität, Horizontbezeichnung und teilweise der Basenzustand. Schlüsselgröße der bodenlagenbasierten Nährkraftbestimmung sind körnungs- und lithochemieabhängige Nährkraftgrundwerte. Die Anwendung des Verfahrens wird unter anderem bei fehlender oder schwieriger Nährkraft-Zuweisung zu Feinbodenformen (z. B. Kippböden, auch meliorierte), der Bearbeitung von Konzept-Standortskarten auf Basis flexibler Profilverläufe und als Vergleichsbasis für methodisch abweichende Bewertungen der Nährkraft von Profilen gesehen.
Die Beurteilung von Standortseigenschaften ist eine der wichtigsten forstwirtschaftlichen Voraussetzungen für eine standörtlich angepasste Baumartenwahl. Die traditionelle Standortskartierung Bayerns klassifiziert forstlich relevante Bodeneigenschaften mit einem nominal- und ordinal-skalierten 3-ziffrigen Standortsschlüssel. Im physiographisch
ausgelegten Bayerischen Standortsinformationssystem BaSIS hingegen werden Bodeneinheiten der ÜBK 1 : 25.000 (Übersichtsbodenkarte des Bayerischen Landesamts für Umwelt) mit quantitativen Bodenkenndaten aus zugewiesenen Leitprofilen belegt (nutzbare Feldkapazität, Trockenrohdichte, volumetrischer Skelettgehalt, Tiefenverlauf der Basensättigung u. a.). Ziel dieser Studie ist es, den gutachterlichen Entscheidungsprozess der terrestrischen Wasserhaushaltsstufen (WHH-Stufen) der Standortskartierung unter Verwendung klimatischer und bodenkundlicher Größen statistisch nachzubilden. Datengrundlage sind 1.349 Profile des Bodeninformationssystems des Bayerischen Landesamts für Umwelt, die mit der Standortskarte und Klimakarten verschnitten wurden. Um die Aussagekraft der WHH-Stufe bezüglich der standörtlichen Trockenstress-Gefährdung zu verstehen, wird das Erklärungsmodell der WHH-Stufen mit zwei deterministischen Trockenstress-Größen unterschiedlich komplexer Wasserhaushaltsmodelle verglichen. Der Vergleich zeigt klar, dass die Transpirationsdifferenz TDiff als eine der beiden deterministischen Trockenstress-Größen und gleichzeitig Grundlage zur Ansprache des Wasserhaushalts in BaSIS wesentlich stärker niederschlagsgetrieben ist als die WHH-Stufe der Standortskartierung. In einem letzten Schritt wird – ermutigt durch eine relativ erfolgreiche Nachbildung der WHH-Stufen – das Potential der WHH-Stufen zur Schätzung der nutzbaren Feldkapazität als einer der wichtigsten bodenkundlichen Kennwerte untersucht. Dabei zeigt sich, dass der Einbezug der Standortskartierung in physiographisch basierte Standortsinformationssysteme die Schätzung dieser Parameter verbessern kann. Für die Praxis-Umsetzung empfiehlt sich, stärker nach den Bodeneinheiten oder aggregierten Bodeneinheiten zu differenzieren und Expertenwissen einzubeziehen. Zusammengefasst stellt diese Studie einen Brückenschlag zwischen den genannten Systemen her. Sie bringt einen Erkenntnisgewinn auf beiden Seiten und unterstützt die Kommunikation zwischen Nutzern des einen oder anderen Systems.
Bodeninformationen gehören zu den zentralen Merkmalen, die im Rahmen der forstlichen Standortskartierung erfasst werden. Die Differenzierung orientiert sich dabei weniger an einer streng bodengenetischen Gliederung (Deutsche Bodensystematik), sondern an forstlich relevanten Merkmalen (Standortsbewertungsverfahren). Dabei erweist sich eine Unterscheidung zwischen relativ stabilen Stammeigenschaften und variablen Zustandseigenschaften als sinnvoll. In den forstlichen Kartiersystemen der Bundesländer werden Bodeninformationen in unterschiedlicher Intensität und Qualität aufgenommen. Diese reichen von der bodenkundlich orientierten Bodenformen- oder Substratkartierung mit umfangreicher laboranalytischer Untersetzung bis zu vegetationsökologisch orientierten Aufnahmeverfahren mit indirekter Abschätzung von Bodeneigenschaften. Auch die Abdeckung der kartierten Waldflächen ist unterschiedlich. Perspektiven für die Bereitstellung von Bodeninformationen aus der Standortskartierung ergeben sich durch die Aufarbeitung und Harmonisierung von Altdaten sowie die Integration von weiteren Geodaten und datenintensiven Methoden aus dem Bereich der digitalen Bodenkartierung.
Im Rahmen der Standortskartierung wurde in den ostdeutschen Bundesländern seit den 1950er Jahren über mehrere Jahrzehnte bis heute einheitlich nach einem einstufigen, kombinierten Verfahren kartiert. Dieser Ansatz umfasst die Erkundung von abiotischen und biotischen Standortsfaktoren. Ein Teil der dokumentierten Ergebnisse, die detaillierten Profilbeschreibungen der Weiserprofile für Lokalbodenformen, welche häufig mit bodenphysikalischen und -chemischen Analysen hinterlegt sind, standen bisher nur analog zur Verfügung. Mit der Digitalisierung und expertenbasierten Harmonisierung dieser Altdaten entstehen wertvolle Grundlagen für die rechnergestützte Verarbeitung und Auswertung für aktuelle Fragestellungen. In Thüringen und Sachsen wurden bisher über 2.600 Bodenprofile mit vorliegenden bodenphysikalischen Laboranalysen im Geografischen Informationssystem verortet. Rund 1.000 sächsische Profile wurden vollständig harmonisiert und enthalten horizontweise und lückenlos die bodenphysikalischen Eingangsgrößen für die Anwendung von Pedotransferfunktionen. Mit dieser Datenbasis wurde das Substratfeuchtekonzept angewendet und damit eine räumlich differenzierte Berücksichtigung der Wasserspeicherfähigkeit von Waldböden für waldbauliche Planungen möglich.
Die Zielsetzung dieser Studie war die Evaluierung von publizierten Pedotransferfunktionen (PTF) zur Abschätzung der Trockenrohdichte (TRD) anhand von Ergebnissen der bundesweiten Bodenzustandserhebung im Wald (BZE II). Verschiedene Funktionstypen wurden mit publizierten Parameterwerten am BZE II-Datensatz geprüft. Viele Funktionen zeigten bei einer unkalibrierten Anwendung einen deutlichen Bias (ME) und einen großen Fehler der prognostizierten Werte im Vergleich zu den Messwerten (RMSE). Dem gegenüber erweisen sich die Funktionen von Alexander (1980), Manrique & Jones (1991) und Tamminen & Starr (1994) über alle Bodentiefen als sehr robust. Die Modellgüte der getesteten Funktionen ließ sich durch eine Neukalibrierung am BZE II-Datensatz z. T. wesentlich verbessern, allerdings zeigten viele Funktionen gerade im Bereich hoher TRD systematische Fehler. Die höchste Modellgüte wurde durch ein einfaches gemischtes additives Modell erreicht, das die organische Substanz, die Tiefenstufe, den Skelettgehalt und die Substratgruppe der BZE II als Eingangsdaten berücksichtigt.
We have determined the crystal structures of two decachlorocyclopentasilanes, namely bis(tetra-n-butylammonium) dichloride decachlorocyclopentasilane dichloromethane disolvate, 2C16H36N+·2Cl−·Si5Cl10·2CH2Cl2, (I), and bis(tetraethylammonium) dichloride decachlorocyclopentasilane dichloromethane disolvate, 2C8H20N+·2Cl−·Si5Cl10·2CH2Cl2, (II), both of which crystallize with discrete cations, anions, and solvent molecules. In (I), the complete decachlorocyclopentasilane ring is generated by a crystallographic twofold rotation axis. In (II), one cation is located on a general position and the other two are disordered about centres of inversion. These are the first structures featuring the structural motif of a five-membered cyclopentasilane ring coordinated from both sides by a chloride ion. The extended structures of (I) and (II) feature numerous C—H⋯Cl interactions. In (II), the N atoms are located on centres of inversion and as a result, the ethylene chains are disordered over equally occupied orientations.
Für die Inventurpunkte der zweiten Bundeswaldinventur (BWI2) im Land Brandenburg liegen umfangreiche Bodenund Standortsinformationen vor, die zum einen direkt aus der Bodenzustandserhebung (BZE) stammen und zum anderen mit Hilfe eines ausgewählten Regionalisierungsansatzes generiert wurden. Es erfolgt eine Verknüpfung der Bestandes- und Bodendaten und eine stichprobenbezogene Modellierung der Standorts-Leistungs-Beziehung für die Baumart Kiefer unter Berücksichtigung des Bestandesalters. Die in unterschiedlichen Teilkollektiven ermittelten Regressionsmodelle liefern bei einem R2-Wert von 0,56 identische Einflussgrößen (Nährkraft, Verdunstung) und vergleichbare Parameterkoeffizienten für die Zielgröße der absoluten Höhenbonität. Im Hinblick auf die Bonitäts-Alters-Beziehung ergibt sich aufgrund allgemein verbesserter Standortsbedingungen ein Vorteil der Jungbestände gegenüber den Altbeständen. Dieser Effekt ist umso stärker, je geringer die Stammnährkraft an einem Standort ist.
Im Rahmen eines Waldklimafonds-Projektes werden auf
Basis von Daten der Bodenzustandserfassung im Wald (BZE) und zusätzlichen Bodenprofilen Bodendaten auf die Traktecken der Bundeswaldinventur (BWI) so übertragen, dass nicht nur die Schätzdaten für die Parametrisierung klimasensitiver Wachstumsmodelle verfügbar, sondern auch deren Fehler abgeschätzt werden. Auf der Basis einer unabhängigen Validierung werden klassische Regressionstechniken (OLS, Regression-Kriging) alternativ zu Random-Forestsund BRT-Modellen getestet. Die Beobachtungsdatenbasis für die Modellbildung stammt aus den Messungen und Bodenbeschreibungen der BZE, anderen Projektdaten und der Forstlichen Standortskartierung. Die Regiogalisierung von 13 Zielgrößen (Skelettgehalt, Trockenrohdichte, %Sand, %Schluff, %Ton, Gründigkeit, nFK, Hydromorphie, C-Gehalt, C/N-Verhältnis, Basensättigung, effektive Kationen Austauschkapazität, pHKCl) wird in 1–2 Bodentiefen durchgeführt, was je 25 Regionalisierungsmodelle in 8 aggregierten Bodengroßlandschaften der BÜK1000 ergibt. Für die Modellanwendung werden individuell für die Charakteristika dieser Straten angepasste Prädiktorensets identifiziert und so die Erklärungsgüte der Modelle maximiert. Dieser Beitrag gibt einen Überblick über die bundesweite Auswertungsstruktur, beschränkt sich für methodische Details und Ergebnisse aber hauptsächlich auf die Region Alpenvorland und Nördliche Kalkalpen. Dabei wird gezeigt: 1. dass eine objektive Abgrenzung von Regionalisierungsregionen anhand der naturräumlichen Variabilität der Zielvariablen innerhalb und zwischen Regionen 2. sowie eine länderübergreifende Regionalisierung trotz unterschiedlicher Datenqualitäten in den Ländern mit vertretbarem Fehlerrahmen möglich ist, 3. und die Auswirkung unterschiedlicher Datenqualitäten auf das Regionalisierungsergebnis quantifiziert werden kann. Bisherige Regionalisierungen von Bodendaten haben gezeigt, dass der Anteil der erklärten Parametervarianz zwischen ca. 50 und 80 % zu erwarten ist, dass die Residuen zufällig verteilt und nicht räumlich autokorreliert sind.
Over the last few decades, considerable attention has focused on small-scale studies of invasive plants and invaded systems. Unfortunately, small scale studies rarely provide comprehensive insight into the complexities of biological invasions at macroscales. Systematic and repeated monitoring of biological invasions at broad scales are rare. In this report, we highlight a unique invasive plant database from the national Forest Inventory and Analysis (FIA) program of the United States Forest Service. We demonstrate the importance and capability of this subcontinental-wide database by showcasing several critical macroscale invasion patterns that have emerged from its initial analysis: (1) large portion of the forests systems (39%) in the United States are impacted by invasive plants, (2) forests in the eastern United States harbor more invasive species than the western regions, (3) human land-use legacies at regional to national scalesb may drive large-scale invasion patterns. This accumulated dataset, which continues to grow in temporal richness with repeated measurements, will allow the understanding of invasion patterns and processes at multi-spatial and temporal scales. Such insights are not possible from smaller-scale studies, illustrating the benefit that can be gained by investing in the development of regional to continental-wide invasion monitoring programs elsewhere.
New Zealand harbours a considerable number of alien plants and animals, and is often used as a model region for studies on factors determining the outcome of introductions. Alien birds have been a particular focus of research attention, especially to understand the effect of propagule pressure, as records exist for the numbers of birds introduced to New Zealand. However, studies have relied on compilations of bird numbers, rather than on primary data. Here, we present a case study of the alien yellowhammer (Emberiza citrinella) introduced from the UK to New Zealand, to demonstrate how recourse to the primary literature highlights significant data gaps and misinterpretations in these compilations. We show that the history of the introduction, establishment and spread of the yellowhammer in New Zealand can be reconstructed with surprising precision, including details of the ships importing yellowhammers, their survival rates on board, the numbers and locations of release, and the development of public perception of the species. We demonstrate that not all birds imported were released, as some died or were re-transported to Australia, and that some birds thought to be introductions were in fact translocations of individuals captured in one region of New Zealand for liberation in another. Our study confirms the potential of precise historical reconstructions that, if done for all species, would address criticisms of historical data in the evidence base for the effect of propagule pressure on establishment success for alien populations.
Non-native rats (Rattus spp.) threaten native island species worldwide. Efforts to eradicate them from islands have increased in frequency and become more ambitious in recent years. However, the long-term success of some eradication efforts has been compromised by the ability of rats, particularly Norway rats (Rattus norvegicus) which are good swimmers, to recolonize islands following eradications. In the Falkland Islands, an archipelago in the South Atlantic Ocean, the distance of 250 m between islands (once suggested as the minimum separation distance for an effective barrier to recolonization) has shown to be insufficient. Norway rats are present on about half of the 503 islands in the Falklands. Bird diversity is lower on islands with rats and two vulnerable passerine species, Troglodytes cobbi (the only endemic Falkland Islands passerine) and Cinclodes antarcticus, have greatly reduced abundances and/or are absent on islands with rats. We used logistic regression models to investigate the potential factors that may determine the presence of Norway rats on 158 islands in the Falkland Islands. Our models included island area, distance to the nearest rat-infested island, island location, and the history of island use by humans as driving variables. Models best supported by data included only distance to the nearest potential source of rats and island area, but the relative magnitude of the effect of distance and area on the presence of rats varied depending on whether islands were in the eastern or western sector of the archipelago. The human use of an island was not a significant parameter in any models. A very large fraction (72%) of islands within 500 m of the nearest potential rat source had rats, but 97% of islands farther than 1,000 m away from potential rat sources were free of rats.