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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.
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.
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.
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.
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.
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.
Status and restoration potential of heathlands and sand grasslands in the southwest of Luxembourg
(2017)
In Europe, semi-natural nutrient-poor ecosystems such as sand grasslands and heathlands have shown extreme declines in surface area and species richness within the last century. The remaining sites are hence of high conservation value. This study analysed the vascular plant species inventory of established and recently restored heathlands and sand grasslands in the southwest of Luxembourg. Analyses to explain differences in vegetation composition between “old” (remnant sites or sites restored a long time ago) and “new” (recently restored) sites in relation to environmental variables were carried out with DCAs and ANOVA/Mann-Whitney-U tests, respectively. The vegetation of old heathlands had few character species of typical heathland communities (Calluno-Ulicetea, Nardetalia), whereas new heathland sites were preponderantly marked by taxa of meso- or eutrophic grasslands and ruderal communities. New heathland sites mainly differed from old sites by higher soil phosphorus contents. Sand grassland vegetation was species-rich and composed by species of the Sedo-Scleranthetea and Festuco-Brometea. With increasing age of the sites, vegetation composition shifted to grass dominance with species of the Molinio-Arrhenateretea. New sand grasslands differed from old sand grasslands by higher soil pH, higher soil potassium content and lower graminoid cover. The differences between new and old sites of both habitat types could mainly be explained by successional processes or were a result of topsoil removal. In some cases, former anthropogenic impact at or in close proximity of restored sites resulted in unsuitable conditions, such as alkaline soil on former landfill sites or highly eutrophic soil due to intensive agriculture. Future management options for the study sites are discussed.
This study describes the vascular flora and community structure of grasslands occurring on heaps of waste rock left by former Zn-Pb mining in relation to the metal content in the soil and other environmental factors. The study was performed on 65 heaps scattered in agricultural land in southern Poland. The sites were described in terms of plant community characteristics, soil physicochemical properties, distance from woodland, altitude and local climate. The number of plant species and proportion of species of the Festuco-Brometea class decreased with increasing heavy metal (Cd, Pb, Zn) content in the soil, and increased with Ca content and pH of the soil. There was a negative relationship between the proportion of the later successional species and heavy metal content in the soil and a positive relationship between plants connected with the earlier stages of succession and metals. Floristic composition was also affected by distance from woodland and height above sea level. The investigated heaps were primarily colonised by native species dispersed by wind, characterised as competitive stresstolerant, ruderal and competitive strategy species. Three types of Carlino acaulis-Brometum erecti (CB) communities were distinguished: CB typicum – dominated by Brachypodium pinnatum, with the highest proportion of calcareous grassland species, CB festucetosum ovinae subass. nova – loose grassland with abundant facultative metallophytes, and the CB rubietosum caesi subass. nova with nutrientdemanding ruderal and woody plants invading from the nearby forest communities. The three subassociations represent different successional stages of Carlino acaulis-Brometum erecti, strongly dependent on both the substrate and spatial relations. The proportions of species traits, especially a high occurrence of endangered species and a very low proportion of alien species show that the post-mining habitats studied have a similar degree of ‘naturalness’ as valuable xerothermic grasslands on nonmetalliferous habitats. They thus may be considered as valuable objects for the protection of plant diversity.
This paper provides a comprehensive survey of the results of phytocoenological research into Alnus incana forests from the alliance Alnion incanae in the Dinarides. Stands from the south-eastern Dinarides (Alnetum incanae = Oxali-Alnetum incanae) were analyzed and compared with those from the north-western Dinarides (Lamio orvalae-Alnetum incanae). The comparison reveals significant differences in the floristic composition and in the degree of differentiation – and particularly in the presence of the species of the Illyrian floristic geoelement. Focus was placed on the area of western Croatia where a geographic variant of Helleborus dumetorum had previously been defined within the association Lamio orvalae-Alnetum incanae. Two of its subtypes, Salix alba and Alnus glutinosa, were determined in our research. The former subtype thrives on occasionally flooded, moist sites, where the floristic composition is dominated by hygrophytes. The latter subtype grows on elevated and drier terraces and is richer in mesophilous species from the surrounding zonal forests. A floristic-sociological comparison of the Lamio orvalae-Alnetum incanae with the related syntaxa indicates the presence of about fourty diagnostic species which accentuate its independence and the need to assess it at the level of an independent, regional association within the alliance Alnion incanae.
The aim of our study was to reveal the differences in the species composition and soil properties of open sandy grasslands dominated by different Festuca species, Festuca vaginata and F. pseudovaginata. Due to the arid conditions, sandy grasslands are generally covered by xerothermic vegetation in which F. vaginata is a typical dominant species. Festuca pseudovaginata, a species newly described by the authors, can also gain dominance in sandy grasslands. However, species composition and soil properties of grasslands dominated by this recently discovered species are still undiscovered. Based on previous coenological studies, we hypothesised that the grasslands characterised by the endemic F. vaginata are more species-rich than those with F.pseudovaginata.
Coenological sampling was carried out in May 2009 at two study sites using the Braun-Blanquet method in quadrats of 2 m × 2 m. Five relevés were sampled in stands dominated by F. vaginata and F. pseudovaginata respectively at two study sites in Central Hungary, resulting in a total of twenty relevés. Analyses were based on the cover scores of vascular plant species and cryptogam crust and values of seven soil properties (pH [KCl], pH [H2O], humus, total N, Ca, P2O5 and K2O) measured in the 0–15 and 15–30 cm soil layers. Soil properties of the grasslands dominated by F. pseudovaginata and F. vaginata (dependent variables) were compared by linear mixed models, where ‘grassland type’ was the fixed factor and ‘site nested in grassland type’ was considered as random factor. Data were analysed by cluster analysis, fusion algorithm was a combinatorial method (minimising increase of variance), and the correlation was used as comparative function. We compared the cover of subordinate species by Mann-Whitney U test. We found that F. pseudovaginata and F. vaginata samples were well separated, and grasslands dominated by F. pseudovaginata had nearly two times more species than those dominated by F. vaginata. Based on the cluster analyses using plant cover and upper 0–15 cm soil layer data, F. pseudovaginata and F. vaginata groups could be well separated. Linear mixed models revealed that F. vaginata grasslands were typical on soils with higher pH, nitrogen, phosphorous and potassium contents compared to F. pseudovaginata grasslands, which indicates a tight connection between the properties of the upper soil layer and the vegetation in sandy grasslands.
Bromus racemosus L. is a rather rare grass species of moist meadows. It has strongly decreased in the course of the 20th century due to intensification of agricultural grassland management, and is therefore included in Red Lists of several European countries. Its winter annual life-cycle is remarkable for a species of permanent grasslands.
The aim of this study is to determine the habitat preference and optimal management of B. racemosus in the Netherlands and surrounding countries. Vegetation, soil and hydrological data from 28 sites in the Netherlands have been compared with B. racemosus cover, and with vegetation data from surrounding countries. The results indicate that B. racemosus is characteristic of Molinio-Arrhenatheretea meadows with good mineralisation and aftermath grazing. The optimum lies in grasslands of the alliance Alopecurion pratensis (Deschampsion cespitosae), but the species ranges from wetter Calthion palustris meadows to drier Arrhenatherion elatioris and Cynosurion cristati grasslands. It prefers intermediate nutrient levels and hydrological conditions (mesic sites), but within this range the highest cover is found in relatively nutrient rich and dry sites. Because of the absence of a seedbank and a low dispersal capability, B. racemosus is vulnerable to changes in grassland management. A management of mowing after 15 June and aftermath grazing is most suitable, since it enables fruit ripening and the maintenance of an open sward, needed for germination and development. The risk of extinction is likely to be higher in flat polders than in floodplain sites with natural relief, where the species may shift between belts in different years.
Vegetation patterns of floodplain forests are highly variable across different habitats in European regions. Their plant communities have been well described from the phytosociological point of view, but plant species richness and composition patterns and their underlying environmental factors are still insufficiently known. Sixty-one vegetation plots of black alder-dominated floodplain forests were sampled in central Slovakia in order to find main environmental predictors affecting floristic diversity of their vegetation. For each vegetation plot with a constant size (400m2), vascular plant species and a set of topographic, climatic, soil physical and chemical characteristics were recorded. A generalized linear model was applied to explain relevance of environmental factors on changes of species richness, whereas the relationship between species composition and explanatory variables was tested using ordination methods. Main gradients of species compositional variation were soil moisture, light, elevation and soil chemistry-related variables. Vascular species richness of plots varied between 19 and 59 (mean 38). Herb-layer species richness was positively related to the soil pH, stream power index and negatively to the concentration of soil iron. These linear trends were accompanied by a hump-shaped response to sand content and a U-shaped response to elevation.
Background: Isolated transient vertigo can be the only symptom of posterior circulation ischemia. Thus, it is important to differentiate isolated vertigo of a cerebrovascular origin from that of more benign origins, as patients with cerebral ischemia have a much higher risk for future stroke than do those with "peripheral" vertigo. The current study aims to identify risk factors for cerebrovascular origin of isolated transient vertigo, and for future cerebrovascular events.
Methods: From the files of 339 outpatients with isolated transient vertigo we extracted history, clinical and technical findings, diagnosis, and follow-up information on subsequent stroke or transient ischemic attack (TIA). Risk factors were analyzed using multivariate regression models (logistic or Cox) and reconfirmed in univariate analyses.
Results: On first presentation, 48 (14.2%) patients received the diagnosis "probable or definite cerebrovascular vertigo". During follow-up, 41 patients suffered stroke or TIA (event rate 7.9 per 100 person years, 95% confidence interval (CI) 5.5–10.4), 26 in the posterior circulation (event rate 4.8 per 100 person years, 95% CI 3.0–6.7). The diagnosis was not associated with follow-up cerebrovascular events. In multivariate models testing multiple potential determinants, only the presentation mode was consistently associated with the diagnosis and stroke risk: patients who presented because of vertigo (rather than reporting vertigo when they presented for other reasons) had a significantly higher risk for future stroke or TIA (p = 0.028, event rate 13.4 vs. 5.4 per 100 person years) and for future posterior circulation stroke or TIA (p = 0.044, event rate 7.8 vs. 3.5 per 100 person years).
Conclusions: We here report for the first time follow-up stroke rates in patients with transient isolated vertigo. In such patients, the identification of those with cerebrovascular origin remains difficult, and presentation mode was found to be the only consistent risk factor. Confirmation in an independent prospective sample is needed.
Functional imaging studies using BOLD contrasts have consistently reported activation of the supplementary motor area (SMA) both during motor and internal timing tasks. Opposing findings, however, have been shown for the modulation of beta oscillations in the SMA. While movement suppresses beta oscillations in the SMA, motor and non-motor tasks that rely on internal timing increase the amplitude of beta oscillations in the SMA. These independent observations suggest that the relationship between beta oscillations and BOLD activation is more complex than previously thought. Here we set out to investigate this rapport by examining beta oscillations in the SMA during movement with varying degrees of internal timing demands. In a simultaneous EEG-fMRI experiment, 20 healthy right-handed subjects performed an auditory-paced finger-tapping task. Internal timing was operationalized by including conditions with taps on every fourth auditory beat, which necessitates generation of a slow internal rhythm, while tapping to every auditory beat reflected simple auditory-motor synchronization. In the SMA, BOLD activity increased and power in both the low and the high beta band decreased expectedly during each condition compared to baseline. Internal timing was associated with a reduced desynchronization of low beta oscillations compared to conditions without internal timing demands. In parallel with this relative beta power increase, internal timing activated the SMA more strongly in terms of BOLD. This documents a task-dependent non-linear relationship between BOLD and beta-oscillations in the SMA. We discuss different roles of beta synchronization and desynchronization in active processing within the same cortical region.
Reactive oxygen species are produced transiently in response to cell stimuli, and function as second messengers that oxidize target proteins. Protein-tyrosine phosphatases are important reactive oxygen species targets, whose oxidation results in rapid, reversible, catalytic inactivation. Despite increasing evidence for the importance of protein-tyrosine phosphatase oxidation in signal transduction, the cell biological details of reactive oxygen species-catalyzed protein-tyrosine phosphatase inactivation have remained largely unclear, due to our inability to visualize protein-tyrosine phosphatase oxidation in cells. By combining proximity ligation assay with chemical labeling of cysteine residues in the sulfenic acid state, we visualize oxidized Src homology 2 domain-containing protein-tyrosine phosphatase 2 (SHP2). We find that platelet-derived growth factor evokes transient oxidation on or close to RAB5+/ early endosome antigen 1− endosomes. SHP2 oxidation requires NADPH oxidases (NOXs), and oxidized SHP2 co-localizes with platelet-derived growth factor receptor and NOX1/4. Our data demonstrate spatially and temporally limited protein oxidation within cells, and suggest that platelet-derived growth factor-dependent “redoxosomes,” contribute to proper signal transduction.
Steilhänge der Mittelgebirge weisen eine kleinräumige standörtliche Vielfalt auf und wurden aufgrund ihrer exponierten Lage bereits frühzeitig durch den Menschen u. a. als Befestigungsanlage genutzt. Daraus resultierte häufig eine hohe floristische und vegetationskundliche Diversität mit hohem Naturschutzwert. Durch Umwelt- und Nutzungsveränderungen hat sich aber auch an diesen Standorten in den letzten Jahrzehnten ein starker Wandel vollzogen. Durch Auswertung alter Florenlisten und Vegetationsaufnahmen und durch aktuelle Erhebungen wollen wir die Vegetationszusammensetzung der Lengder Burg, eines Steilhangs auf Unterem Muschelkalk im südlichen Göttinger Wald (Süd-Niedersachsen, Deutschland), und ihre Veränderung aufzeigen und Rückschlüsse für die zukünftige Behandlung ziehen. Dazu wurden Angaben zur Gefäßpflanzenflora aus dem Zeitraum 1950 bis 1995 mit einer aktuellen floristischen Kartierung des Gesamtgebiets von 2016 verglichen. Die Vegetationszusammensetzung wurde anhand von 37 Vegetationsaufnahmen aus dem früheren Zeitraum harakterisiert. 29 dieser Flächen wurden 2009 bis 2016 erneut aufgenommen. Räumliche und zeitliche Unterschiede in der Diversität und Artenzusammensetzung wurden hinsichtlich verschiedener standörtlicher Parameter und ökologischer Artengruppen analysiert.
Die Vegetation lässt sich zwei Gruppen zuordnen: 1. Das Carici-Fagetum und seine Kontaktgesellschaften an südlich und westlich exponierten Steilhängen. 2. Das Hordelymo-Fagetum mit verschiedenen Ausbildungen auf dem Plateau und an flacheren Süd- und Nordhangbereichen. Im Carici-Fagetum ist ein deutlicher Diversitätsverlust und eine Zunahme in der Dominanzstruktur der Krautschicht zu erkennen, der im Vergleich der Aufnahmezeiträume auf eine zunehmende Homogenisierung der Vegetation hinweist. Zurückgegangen sind dabei besonders die typischen Kenn- und Trennarten dieser Waldgesellschaft bei gleichzeitiger Zunahme der Buche in der Verjüngung. Im Hordelymo-Fagetum bewirkt neben Gehölzen in der Strauch- und Krautschicht vor allem die Zunahme von Allium ursinum eine homogenere Artenzusammensetzung, jedoch ohne Diversitätsverlust. Neben Stickstoffeinträgen, dem Klimawandel sowie einem reduzierten Rehwild-Verbiss bedingt besonders der Nutzungswandel diese Veränderungen. Vor allem im Carici-Fagetum wirkte sich der Übergang zwischen früherer Nieder- und Mittelwald-Nutzung mit Waldweide über eine fast 100jährige Hochwald-Nutzung bis zum jetzigen Schutzwald stark aus. Gleichwohl weisen die steilen Hänge weiterhin einen hohen Anteil an Rote-Liste-Arten auf und tragen wesentlich zur hohen Biodiversität des Gebiets bei. Veränderungen in der Vegetation der Lengder Burg spiegeln die Veränderungen im Göttinger Wald insgesamt wider. Kleinflächige Offenhaltungsmaßnahmen zur Erhaltung wertvoller floristischer Elemente sind teilweise erfolgreich. Kleinwüchsige, lichtbedürftige Magerkeitszeiger verschwinden jedoch zunehmend aus den sich entwickelnden, hochwüchsigen Stauden-Säumen. In den benachbarten, unbewirtschafteten Hangbuchenwäldern sorgt die fehlende Nutzung nach Jahrhunderten der Auflichtung und Aushagerung für eine Sukzession in Richtung mesophilen Kalkbuchenwalds.
In Borstgrasrasen (Nardetalia) des Werra-Meißner-Gebietes (Nordhessen, Südniedersachsen) wurden 2012 nach 25 Jahren auf möglichst gleichen Untersuchungsflächen (quasi-Dauerflächen) Wiederholungsaufnahmen angefertigt, um den gegenwärtigen Zustand bzw. Veränderungen in diesem prioritären FFH-Lebensraumtyp zu erfassen. Es wurden insgesamt 61 Flächen untersucht. Neben der Artenzusammensetzung wurden auch Bodenparameter (pH, C/N-Verhältnis, Mächtigkeit der organischen Auflage) und die Nutzung erfasst.
Bei der Wiederholungsaufnahme 2012 waren, abgesehen von einer Aufforstungsfläche, noch auf allen Flächen Arten der Borstgrasrasen vorhanden. Die Flächen wurden 2012 überwiegend genutzt oder gepflegt, während 1986/87 Brachflächen noch bei weitem dominierten. Eine Düngung der Flächen erfolgte nicht. Trotz dieser generell günstigen Nutzungssituation lässt sich ein genereller Trend zur Eutrophierung feststellen, der sich hinsichtlich Artenzahl und Deckung in einer Zunahme von Arten des Wirtschaftsgrünlandes (Molinio-Arrhenatheretea) bei gleichzeitiger Abnahme der Borstgrasrasen-Kennarten äußert. Auch die Artenzahlen der übrigen Magerkeitszeiger nahmen im Mittel ab, während Verbrachungszeiger im Allgemeinen zunahmen. Eine Veränderung der Gesamtartenzahl war nicht festzustellen. Die mittleren Zeigerwerte spiegeln die Verschiebungen im Arteninventar durch erhöhte mittlere Reaktions- und Stickstoffzahlen wider. Strukturell hat in den vergangenen 25 Jahren vor allem eine generelle Zunahme der Moosschichtdeckung und eine Ausbreitung der Sträucher auf Brachflächen stattgefunden. Bei den Bodenparametern waren 2012 eine signifikante Erhöhung der pH-Werte, eine Einengung der C/N-Verhältnisse und eine Abnahme der Mächtigkeit der organischen Auflage (Of) feststellbar. Regressionsmodelle zeigen, dass dabei die Zunahme von Arten des Wirtschaftsgrünlandes direkt mit den ansteigenden pH-Werten zusammen hing, während die Veränderungen bei den Kennarten eher vom Ausgangs-C/N-Verhältnis, teilweise auch von der Entwicklung der organischen Auflage und der Nutzung abhängig waren. Die vorgefundenen Veränderungen werden vor dem Hintergrund möglicher Gefährdungsszenarien (Brache, Eutrophierung, Bodenversauerung, Klimawandel) diskutiert. Angesichts des unerwarteten Befundes einer Eutrophierung bei gleichzeitig nachlassender Bodenversauerung, wird die Hypothese aufgestellt, dass der seit den 1990er-Jahren erfolgte Rückgang der Schwefeldepositionen mit nachfolgender Erholung der Boden-pH-Werte und nachlassender Stressbelastung, z. B. durch Ammonium-Toxizität, die Veränderungen ausgelöst haben könnte. Außerdem deuten die Ergebnisse auf eine zumindest teilweise zu geringe Nutzungs- bzw. Pflegeintensität bzw. zu späte Nutzungstermine. Möglicherweise führt der erhöhte Eutrophierungsdruck hier auch zu verstärkten Anforderungen an das Management der Flächen. Eindeutige Indizien für klimabedingte Veränderungen im Arteninventar ließen sich nicht finden. Indirekte Effekte über eine erwärmungsbedingte Förderung der Mineralisationsraten oder ein ursächlicher Zusammenhang zwischen höheren Wintertemperaturen und der Zunahme der Moosdeckung lassen sich jedoch nicht ausschließen.
Transitional between the Pannonian Basin and the Eastern Carpathians the Transcarpathian Ukraine (Transcarpathia) has a diverse geology including Quaternary sediments, volcanites, limestones and flysch, and its climate at low altitudes is relatively warm and humid. We conducted a field survey in June 2016 focusing on mesophilous forest vegetation along a transect covering almost the whole lowaltitudinal part of Transcarpathia. We recorded 54 relevés in the field and further digitized 22 relevés from literature. Using classification analysis, we distinguished three clusters of oak-hornbeam forests (alliance Carpinion betuli; 1–3) and three clusters of scree and ravine forests (alliance Tilio platyphylli-Acerion; 4–6): (1) Slightly wet Pannonian oak-hornbeam forests occurring in the lowland part of the region (Circaeo-Carpinetum); (2) Mesophilous oak-hornbeam forests (Carici pilosae-Carpinetum); (3) Xero-mesophilous oak-hornbeam forests (a drier subtype of the Carici pilosae-Carpinetum and the association Primulo veris-Carpinetum); (4) Mesophilous scree forests (Phyllitido-Aceretum); (5) Forests of steep slopes (Aceri-Tilietum) and transitions to mesophilous oak-hornbeam forests (Carici pilosae-Carpinetum); (6) Cool and wet scree and ravine forests (Arunco dioici-Aceretum pseudoplatani). Using indirect ordination analysis, three environmental variables (altitude, heat load index and slope) were identified as factors of significant influence on the species composition. These factors well distinguish oak-hornbeam forests from scree and ravine forests.
Understanding plant-plant interactions is essential in planning and implementing effective grassland management strategies. Positive and negative interactions generally co-occur in plant communities and the net effect of these interactions may depend on the disturbance regime, including grazing. Shrubs can act as biotic refuges by physically protecting neighbouring plants from herbivores. As a result, we would expect that in pastures the diversity and flowering success of plants is higher in the close vicinity of shrubs compared to the open vegetation. Nevertheless, we can also assume a competitive trade-off cost for plants that grow together with shrubs. In this study, we assessed the small-scale effects of dwarf shrubs (30–40 cm in diameter) on species density and flowering success. Specifically, we considered three types of microsites: (i) shrub interior, (ii) edge of shrub, and (iii) open pasture (more than 2 meters away from the shrub). We surveyed these three types of microsites using 10 × 10 cm sized plots both in grazed and ungrazed meadow steppe, in central Hungary. The highest species density was found at the edge of shrubs, both in grazed and ungrazed vegetation. Meanwhile, species density did not differ significantly between shrub interiors and the open pasture. However, in grazed vegetation, species flowering success was significantly higher in shrub interiors and edges than in the open pasture; no significant trend was observed for this measure in ungrazed vegetation. In contrast to previous studies, we did not detect a competitive effect of small-sized shrubs on plants in ungrazed vegetation. Our results indicate that small-sized shrubs protect other plants from herbivores and that the edge effect plays an important role for the maintenance of small-scale species diversity in pastures. Overall, our results underline the beneficial effect of biotic refuges in pastures and we suggest that retaining a sparse population of small-sized native shrubs is advantageous from a conservation point of view.
The influence of the Eastern migration route on the Slovak flora – a comparison after 40 years
(2017)
Transport is an important source of introduction and spread of alien plants into new areas and countries. This study provides comprehensive research of selected railway localities in South-Eastern Slovakia to determine the influence of the Eastern Migration Route on the Slovak flora. Railway transshipment yards in Čierna nad Tisou, Dobrá, Velké Kapušany and Matovce were studied from 1964 to 2013; with historic data sampled 1964–1998 and recent data sampled 2012–2013. These data sets were compared to determine differences in species structure following the decreased use of the transshipment yards.
A total of 657 vascular plant taxa were recorded in all localities (566 taxa in the historic and 431 taxa in the recent data set). Native species prevailed over aliens and archaeophytes over neophytes in both time periods. The most frequent aliens were naturalised taxa, where Asiatic and European species prevailed. The most frequent families were Poaceae, Asteraceae and Brassicaceae, and while many species introduced with Russian wheat were recorded only in the past, several taxa are also recorded only recently. Hemicryptophytes were the most abundant life form. Most recorded species were competitors, reproducing by seed and pollinated by insects. Zoochory and hemerochory were the most frequent dispersal types. The proportion of species traits has not changed over time. We identified 49 threatened taxa (38 in the historic and 27 in the recent data set). The Eastern migration route significantly increases the species number of alien vascular plants in the Slovak flora. Although this route had much greater importance in the past, when the role of the Eastern Slovak trans-shipment railway yards was much higher, the studied yards remain an important gateway to Eastern Central Europe and they continue to support agestochory migration of adventive plants.
Wet grasslands once covered a large area in the lowlands of northern Germany, but have declined since several decades as a result of land use intensification. Permanent plot data from such grasslands in the region that would allow to assess the extent of changes in species composition and richness are still rare. Here, we present a re-visitation study of 52 quasi-permanent plots from the Stedinger Land area in the basin of the river Weser near Bremen, comparing quadrat data between 1948 and 2015. In 1948, the grasslands were characterized by species typical of wet, moderately fertile grasslands belonging to the Bromo-Senecionetum aquatici (Bromion racemosi), including 15 species currently classified as threatened. Until 2015, the vegetation had changed strongly: almost all indicators of wet grasslands had either declined or completely vanished, whereas more nutrient-demanding species of less wet soils had increased, especially grasses. The cumulative number of species had declined by 50%, while mean plot species richness had decreased by 64.6%, mainly resulting from the pronounced loss of many herbs. A comparison of mean Ellenberg indicator values suggested that the plots had become drier, but also more base- and nutrient-rich, most likely triggered by the intensification of land use with drainage and fertilization as well as more frequent and earlier cutting. Our study reflects the dramatic loss of plant species diversity in wet grasslands over the past 60−70 years in areas not preserved and properly managed, and it documents the need for protecting remnants of these grasslands and for restoring wet grassland areas by re-wetting, nutrient removal and the transition to a less intensive land use.
Marginal associations, i.e. floristically impoverished associations at the margin of the distribution area of a higher syntaxon, form a problem in vegetation classification, because true character species are lacking. We propose a new approach for the classification of such marginal associations, making use of the notion of 'chorological tension zones'. In the absence of true character species, the species from other syntaxa of the same formation can be used as such. Our proposal is to use the species group from every formation-true class only once within every marginal alliance, to limit the number of possible marginal associations. This approach is illustrated in a classification of the retamoid thickets in the Netherlands. On the basis of a numerical-subjective classification of the relevant species in the scrub layer and the evaluation of relevant literature, we conclude that the broom and gorse thickets in the Netherlands can be assigned to the Cytisetea scopario-striati Rivas-Mart. 1974, which is represented by four associations, each of which is characterised by the species of other scrub classes. The Ulici europaei-Sarothamnion scoparii Doing ex Weber 1997 is represented by the Rubo plicati-Sarothamnetum scoparii Weber 1987 and the Crataego monogynae-Cytisetum scoparii R. Haveman, I. de Ronde & J.H.J. Schaminée ass. nov., the Ulici europaei-Cytision striati Rivas-Mart., Báscones, Díaz, Fern. Gonz. & Loidi 1991 by the Frangulo alni-Ulicetum europaei De Foucault 1988 and the Rubo ulmifolii-Ulicetum europaei J.-M. Géhu ex R. Haveman, I. de Ronde & J.H.J. Schaminée ass. nov. This classification is based on a restricted dataset though, and a revision, based on a larger dataset from a wider region has to prove the tenability of the classification.
Extensively managed pastures harbour rare and endangered species and have a decisive role in maintaining grassland biodiversity. Traditional herding of local robust cattle breeds is considered as a feasible tool for preserving these habitats. We studied the scale-dependent effects of grazing on the species richness and composition of three dry grassland types in the Great Hungarian Plain: Achilleo setaceae-Festucetum pseudovinae and Artemisio santonici-Festucetum pseudovinae alkaline grasslands, and Potentillo arenariae-Festucetum pseudovinae sand grassland. We asked the following questions: (1) Does extensive grazing have a scale-dependent effect on plant species richness of alkaline and sand grasslands? (2) How does grazing affect the proportion of specialists, generalists and weeds in the three grassland types? We sampled ten sites of each grassland type, including five extensively grazed and five non-grazed sites (altogether we had 30 sites). We used a series of nested plots each consisting of 10 plots from the size of 0.01 m² to 16 m². We revealed that grazing has contrasting effects in the three grassland types, and had a considerable effect on their species richness even at small scales. In both alkaline grassland types, total species richness was overall higher in grazed plots but it increased in a similar manner for both ungrazed and grazed habitats across plot sizes. Small-scale heterogeneity likely due to the uneven distribution of grazing, trampling and defecation together with mitigated rate of competition allowed more species to co-exist even at small scales in grazed alkaline grasslands. Grazing increased the richness of specialists, but likely due to the salt stress, establishment of weeds was hampered. Open gaps formed by trampling likely supported the establishment of several specialist species such as Plantago tenuiflora and Puccinellia limosa which are typical to open alkali grasslands. Contrary, in sand grasslands, we did not detect any effect of grazing on total species richness, likely due to the adverse effect of grazing on the species richness of specialists and weeds. In contrast with the former findings we detected significantly higher species richness in 0.01 m² and 0.0625 m² plots in the grazed sand grasslands, but found no differences at larger scales. Whilst species richness of specialists was significantly decreased, richness of weeds was increased by grazing. Decrease in the specialist species richness was likely due to the lack of their evolutionary adaptation to grazing. Degradation caused by grazing and trampling together with the propagule pressure from the neighbouring anthropogenic habitats resulted in an increased richness of weeds in the grazed sites.
The vast majority of European grasslands strongly depend on the regular removal of aboveground biomass by agricultural land use, mostly grazing or mowing or a combination of both. These specific management schemes have strong influence on plant diversity and vegetation composition, depending on their particular characteristics and their intensity. For example, the presence or absence of fertilization will favour some species over others, changing plant communities accordingly. Additionally, the farmer’s choice of a specific management scheme will also depend on the abiotic site conditions. This leads to a complex set of associated factors potentially affecting the structure and diversity of grasslands.
In this study, we compiled a unique dataset of 169 differently managed grasslands (in total 202 plots), which were sampled in five regions across Germany. For each plot, we documented management characteristics, measured plant diversity and functional group composition, recorded endangered species according to red lists, and calculated Ellenberg indicator values. We assessed patterns in vegetation composition and diversity in relation to the particular management scheme, which was categorized as meadow, meadow with autumn or winter grazing (with mowing as predominant management), mown pasture (where mowing and grazing are used at roughly equal intensity), seasonal pasture (with grazing as predominant management) and year-round pasture.
Our study showed that grasslands of different management schemes significantly differed in diversity, structure and functional composition. However, it also became obvious that vegetation composition was not strictly distinguished by management alone. Local and regional characteristics such as soil conditions, size of the grassland species pool or land-use history, often played a more prominent role than land use alone. Assumingly, the interplay of those local and regional characteristics with the proportion of grazing and mowing at a particular site inhibit clear differences among our predefined management schemes. Nevertheless, species richness was the lowest in year-round pastures, moderate in meadows and highest in seasonal pastures. In contrast, year-round pastures harboured the highest mean numbers of endangered species. The dependency of a certain management scheme on site-specific environmental factors such as soil fertility, further complicated the clear separation of management effects from those of the environmental background. In summary, modern grassland management strongly shaped grassland vegetation, but today’s combination of different management practices complicated the assessment of specific land-use effects on plant diversity. Thus, neither mowing nor grazing turned out to be “the one and only” management for nature conservation. Although our results challenge long-term prognoses for future vegetation development under modern grassland management, we clearly showed that low-intensity management and the absence of fertilization promoted plant diversity, with higher values in pastures compared to meadows and mown pastures.
Die in Amerika heimische Kolumbianische Zwergwasserlinse (Wolffia columbiana) tritt neuerdings in Europa als Neophyt auf und konnte in Niedersachsen zum ersten Mal im Jahr 2016 nachgewiesen werden. Im Hintergrund stehen die für den Naturschutz relevanten Fragen, wie viele vermeintliche Vorkommen von Wolffia arrhiza in Wirklichkeit Wolffia columbiana repräsentieren und ob dieser Neophyt die heimische und gefährdete Art Wolffia arrhiza verdrängen kann.
Die Floristisch-soziologische Arbeitsgemeinschaft wurde am 13. August 1927 in Göttingen gegründet und besteht nun, mit einer Unterbrechung zwischen 1941 und 1948, seit 90 Jahren. In diesem Rückblick wird vor allem die Entwicklung nach dem 2. Weltkrieg näher dargestellt. Hauptkapitel sind Verein, Satzung und Vorstände, Mitgliederentwicklung, Jahrestagungen, Arbeitskurse und Workshops, die Publikation der Mitteilungen und von Tuexenia mit ihren Beiheften sowie der Synopsis der Pflanzengesellschaften Deutschlands. Insgesamt wird eine sehr erfolgreiche Entwicklung mit Konstanz wesentlicher, schon zu Beginn formulierter Ziele und dynamischen Anpassungen an neue Gegebenheiten festgestellt.
GrassVeg.DE – die neue kollaborative Vegetationsdatenbank für alle Offenlandhabitate Deutschlands
(2017)
Der Bericht stellt die neue kollaborative Vegetationsdatenbank GrassVeg.DE (EU-DE-020; http://bit.ly/2qgX208) vor, die Vegetationsaufnahmen von Grasländern und anderen nicht-aquatischen Offenlandhabitaten Deutschlands sammelt, um sie national und international für die vegetationsökologische Forschung zur Verfügung zu stellen. GrassVeg.DE trägt die Daten zum European Vegetation Archive (EVA) und künftig auch zur globalen Vegetationsdatenbank „sPlot“ bei. Datenlieferanten von GrassVeg.DE behalten volle Verfügungsgewalt über ihre Daten und werden Mitglied des GrassVeg.DE-Konsortiums. Dadurch profitieren sie durch Co-Autorenschaften und Zitate von ihren Beiträgen und erlangen zugleich die Möglichkeit, selbst Projekte zu beantragen, die GrassVeg.DE- oder EVA-Daten nutzen. Die schnell wachsende GrassVeg.DE-Datenbank umfasste im Juli 2017 3.181 Vegetationsaufnahmen aus acht deutschen Bundesländern. Perspektivisch kann GrassVeg.DE dazu beitragen, eine konsistente Neuklassifikation der Graslandvegetationstypen Deutschlands im Rahmen der Synopsis der Pflanzengesellschaften Deutschlands zu ermöglichen. Wir schließen den Beitrag mit einem Aufruf, eigene und aus der Literatur digitalisierte Vegetationsaufnahmen zu GrassVeg.DE beizutragen.
Seit 12 Jahren werden von Mitgliedern der Eurasian Dry Grassland Group (EDGG) und deren Vorgängerorganisationen Grasland-Sonderteile in Tuexenia herausgegeben. Der diesjährige Sonderteil enthält fünf Artikel, die das Grasland verschiedener mitteleuropäischer Länder mit unterschiedlichen Zielen untersuchen. Der erste Artikel untersucht Auswirkungen von Weide und Mahd auf die Diversität des Graslands in Deutschland in Abhängigkeit von verschiedenen Umweltfaktoren, der zweite die Auswirkung kleiner Büsche auf den Artenreichtum von Gefäßpflanzen in beweideten Wiesensteppen in Ungarn. Der dritte Artikel fragt, ob sich ungarische Sandtrockenrasen mit Festuca vaginata von solchen mit F. pseudovaginata in ihrer Vegetation und ihren Standortsbedingungen unterscheiden; die letztere war erst kürzlich beschrieben worden. Der vierte Artikel modelliert Auswirkungen des Klimawandels auf geschützte Graslandbestände in Serbien und deren Arten während schließlich der fünfte Artikel die Initiative einer neuen Datenbank des deutschen Graslands (GrassVeg.DE) vorstellt und dazu aufruft, sich daran zu beteiligen. Insgesamt haben zu diesem 12. Grasland-Sonderteil 41 Autoren aus fünf Ländern (Dänemark, Deutschland, Italien, Schweiz, Serbien und Ungarn) beigetragen.
Ants were shown to be significant pollinators of two orchid species in the alpine zone of the Alps. Repeated observations from several localities confirm the ant Formica lemani as pollinator of Chamorchis alpina whereas Formica exsecta is reported here for the first time as pollinator of Dactylorhiza viridis. These findings appear of great interest, as significant ant pollination of orchids is unknown so far from any other region or habitat type in the Holarctic. This raises the question if there are specific adaptations. The observations do not provide suggestions to adaptations of the Formica ants for pollinating orchids – they simply followed their normal foraging behavior shown in any type of habitat. Yet, special adaptations are given by the two orchid species in developing pollination mechanisms more strongly involving ground-moving insects which are not inactivated by increased wind velocity and lower temperatures in the alpine zone. These are mainly beetles and ants. The pollination mechanisms and interactions with ants of both orchid species are described. Dactylorhiza viridis is outstanding among orchids in needing 20 to 30 minutes for the 90-degree forward bending of the pollinium after attachment to the insect’s forehead whereas the same process takes place between 15 seconds and 3 to 5 minutes in other orchids. Forward bending of pollinia is required for precise placement of the pollen at the stigmatic surface of another flower. The very long bending time is an adaptation to the longer presence time of ground-moving insects at the same plant and aims to reduce the frequency of geitonogamy (self-fertilization). The high frequency of ant pollination in these orchids is a consequence of the high activity density of aggressive, predatory worker ants leading to a displacement of other pollinators. Attempts of ants to remove the fresh, strongly adhesive pollinia from their foreheads failed and a single ant head could carry up to eight pollinia.
Intense direct and indirect human pressure has been imposed on grasslands throughout their range. Mostly due to the constant need for more food production or due to changes in environmental conditions, grasslands as habitats are expected to become highly endangered. The aim of this study was to estimate the grasslands’ ecological response to future climate and environmental changes. The study took place in three ecologically different grassland communities in three protected natural areas of Serbia (Southeastern Europe), following the same methodology. The study sites were: 1) Peštersko polje Special Nature Reserve (SNR), 2) Deliblato sands SNR (its southern part: Labudovo okno) and 3) Zasavica SNR.
Climate change was simulated for mean temperatures and precipitations using the Eta Belgrade University-Princeton Ocean Model (EBU-POM) climate model, for the A1B Intergovernmental Panel on Climate Change (IPCC) emission scenario covering the 1951–2100 period and insolation and volumetric soil moisture content for the 1979–2100 period. Grassland vegetation was analysed at all three sites. One representative plant community per site was selected for further analysis and simulation of ecological changes. One plot was positioned inside each of the above-mentioned communities, all vascular plant species inside the plot were recorded, and soil samples were taken. Ecological Optima (EO) for moisture and temperature were calculated from modified Ellenberg’s plant indicator values of recorded species. The plants’ response to climate and environmental changes was simulated using the VSD+ model for the 2010–2100 period. The data obtained from the model were further analysed with Canonical Correspondence Analysis (CCA).
Overall results show that the temperature rise, along with the irregular precipitation at all three sites, will lead to a drop of the relative abundance of many native species in the period between 2040 and 2060. The low obtained Habitat Suitability Index for the future means that there will be either unfavourable environmental conditions for the development of grasslands, or the species we analysed were untypical. Cosmopolitans and xerothermic species will be more accustomed to the new conditions. Grasses will be the most resilient functional group according to our study. It may be concluded that the functional group of grasses will also play the leading role in future
grasslands at the studied sites.
Central European temperate forests are – with the exception of floodplain forests – relatively little invaded by alien plants. However, despite substantial recent progress, there is still a lack of using vege-tation plot data for analyzing spatio-temporal patterns of alien tree species invasions.
We calculated relevé-based metrics of tree species’ ecological preferences using 19,413 phytosociological forest relevés of the Austrian vegetation database. We focused on the five most widely distributed alien trees, i.e. two archaeophytes (Castanea sativa, Juglans regia) and three neophytes (Acer negundo, Ailanthus altissima, Robinia pseudoacacia). For each of these species we analyzed the mean cover in the tree layer and the occurrence in the herb and shrub layers in relevés colonized by adult trees as a measure for persistence. Further, we evaluated the intergenerational ecological plasticity (= the ability of young trees to grow under different site conditions than adults) for the tree species, and the mean relevé indicator values for light, nutrients, moisture and hemeroby. We then compared these alien and native tree species metrics.
We found that A. altissima and R. pseudoacacia build up high mean cover values in invaded forests, but this was not the case for the other alien trees. Thus, both species strongly affected forest communities of invaded sites. Similarly, the two species were common in the lower vegetation layers indicating recruitment under the canopy of adult conspecifics; this was facilitated by their ability to produce root suckers. Highest values of inter-generational ecological plasticity occurred in native pioneer trees and species of softwood floodplain forests, while alien trees had moderately high (A. negundo, A. altissima, J. regia) to low values (C. sativa, R. pseudoacacia). With the exception of C. sativa, all alien species showed high mean Ellenberg indicator values for light and nutrients, and were more common in sites with high hemeroby and high mean Ellenberg indicator values for temperature. Distinct from the ecological preferences of alien trees, and thus rarely invaded, were montane beech forests, coniferous mountain forests and forests at extremely dry sites, as well as swamp and bog forests dominated by willows and ash.
We conclude that relevé-based metrics of the behavior of alien tree species allow new insights into the spatio-temporal dynamics of invasion of woody species in forests. Future work should expand this approach, e.g., by considering the role of life history traits and actual site conditions.
The flora in the Caucasus Ecoregion is rich in economically important plants. While its value in terms of food crops and medicinal plants has recently been subject to scientific research, the ornamental value of many Caucasian plant species has not yet been fully recognized. In order to assess the ornamental value of the Caucasian flora, vegetation data from two mountainous study regions in Georgia (n = 958 species, mostly grassland vegetation) was compared with the product range of ornamental plants in Germany using an online plant shopping guide. Characterization of the 150 plant species listed in both databases revealed that 121 species are present in central Europe and 117 species are natives or archaeophytes in Germany. Thus, only few species are Caucasian endemics. Furthermore, a list of 79 potential ornamentals endemic to the Caucasus was compiled from the literature. In order to place them in context of the horticultural market, the species characteristics were examined. Following this, a critical discussion of the potentials and risks arising from trade with ornamental plants was carried out with regard to nature conservation, biological invasion control, genetic resource maintenance and socioeconomic significance.
Der Zwerg-Rohrkolben (Typha minima Funck ex Hoppe) ist eine charakteristische Pionierpflanze von alpinen Wildflusslandschaften. Seit den siebziger Jahren ist diese Kennart jedoch in Deutschland vollständig und in Österreich nahezu ausgestorben. Die anhaltenden Populationsrückgänge der Art sind wahrscheinlich das Ergebnis der weitverbreiteten Flussregulierung und des Kraftwerksbaus in Kombination mit den sehr speziellen Standortsansprüchen der Art. Dank den Anstrengungen von Wiederansiedlungsprogrammen befindet sich T. minima wieder an der Oberen Drau in Österreich. In dieser Publikation wird über die Keimung, das Wachstum, die Reproduktion und die Umweltpräferenzen von T. minima berichtet.
Die Keimungsexperimente von 2014 zeigten eine sehr niedrige mittlere Keimungsrate von 15,6% bei einem Schwankungsbereich von 0–90 %. Die Keimungsraten stiegen mit höheren Temperaturen, erhöhter Saatgutreife und kürzeren Saatgutlagerungszeiten. Nach der Saatgutlagerung von 480 Stunden wurde keine Keimung mehr beobachtet.
Beim FFH-Monitoring 2014 an der Oberen Drau wurden Zwerg-Rohrkolben-Keimlinge (Höhe < 5 cm) generell nur selten gefunden. Die vegetative Jungphase (Höhe > 15 cm, ausschließlich sterile Triebe) wies zumeist den höchsten Flächenanteil im Mittel von 62% auf. Typha minima bildete bis zu einem Alter von ca. 3 Jahren ausschließlich sterile Triebe aus. Ab einem Alter von ca. 9 Jahren wurden auch fertile Triebe mit Blütenständen ausgebildet, wobei deren Anzahl mit zunehmendem Alter sich tendenziell erhöhte. Die Analyse der Standortsfaktoren zeigte, dass T. minima auf eine hohe Bodenfeuchte im Mittel von 39 Vol-% angewiesen ist. Darüber hinaus war der Faktor Beschattung entscheidend. Erst ab einem Beschattungsgrad von 50% durch Weidengebüsche war eine Abnahme der Triebdichte von T. minima zu verzeichnen. Wir schließen daraus, dass T. minima-Populationen während der Keimungsphase extrem empfindlich sind und dass massive Habitatverluste überwiegend das Ergebnis der Flussregulation und der reduzierten Morphodynamik sind, die normalerweise geeignete offene Siedlungsräume für die Keimung des Zwerg-Rohrkolbens schaffen würde.
The view that tumors consist of a homogenous mass of clonal derived cells has dramatically changed in recent years. Tumors harbor an enormous heterogeneity of cells with distinct capabilities and functions. The heterogeneity originates from a differentiation hierarchy of tumor cells, similar to normal tissue organization of stem-cell driven organs, but also from clonal succession of subpopulations by randomly acquired genetic mutations and epigenetic changes. Both scenarios are certainly not mutually exclusive, and also stem and progenitor cells underlie mutational selection. Intratumoral heterogeneity is a major challenge for cancer treatment and disease monitoring. Functional studies revealed that not all tumor cells have the same ability to initiate tumor growth upon transplantation in receptive animal models. The tumorinitiating cells (TICs) were called cancer stem cells due to their similarities to normal tissue stem cells in their molecular and functional properties. They can renew themselves long-term and give rise to tumor cells lacking cancer stem cell properties. However, it is worth stressing here that TICs do not necessarily originate from stem cells, but may have regained stem cell properties. TICs caught major attention since they may provide important steps in the progression of malignant diseases, such as epithelial-to-mesenchymal transition, dissemination, long-term persistence, therapy resistance, and relapse of the disease. The prospective identification of TICs using distinct surface markers would allow their molecular and functional characterization, the design of detection methods for diagnosis and prognosis, and the development of targeted therapies against these detrimental cells. While functional evidence for the existence of TICs were provided for many tumor entities, their marker profile still remains largely undefined and controversial. ...
Purpose: To evaluate long-term outcome of three years and treatment patterns of patients suffering from severely drug-refractory epilepsy (SDRE).
Methods: This analysis was population-based and retrospective, with data collected from four million individuals insured by statutory German health insurance. ICD-10 codes for epilepsy (G40*) and intake of anticonvulsants were used to identify prevalent cases, which were then compared with a matched cohort drawn from the population at large. Insurance data were available from 2008 to 2013. Any patient who had been prescribed with at least four different antiepileptic drugs (AEDs) in an 18-month period was defined as an SDRE case.
Results: A total of 769 patients with SDRE were identified. Of these, 19% were children and adolescents; the overall mean age was 42.3 years, 45.4% were female and 54.6% male. An average of 2.7 AEDs per patient was prescribed during the first follow-up year. The AEDs most commonly prescribed were: levetiracetam (53.5%), lamotrigine (41.4%), valproate (41.3%), lacosamide (20.4%), and topiramate (17.8%). During 3-year follow-up, there was an annual rate of hospitalization in the range 42.7 to 55%, which was significantly higher than the 11.6–12.8% (p < 0.001) for the matched controls. Admissions to hospital because of epilepsy ranged between 1.7 and 1.9 per year, with an average duration for each epilepsy-caused hospitalization of 10–11.1 days. The number of comorbidities for SDRE patients was significantly increased compared with the matched controls: depression (28% against 10%), vascular disorders (22% against 5%), and injury rates were also higher (head 16% against 3%, trunk and limbs 16% against 8%). The 3-year mortality rate for SDRE patients was 14% against 2.1% in the matched cohort.
Conclusion: SDRE patients are treated with AED polytherapy for all of the 3-year follow-up period. They are hospitalized more frequently than the general population and show increased morbidity levels and a sevenfold increase in mortality rate over 3 years. Further examination is required of ways in which new approaches to treatment could lead to better outcomes in severely affected patients.
Background: CML presenting with a variant Philadelphia translocation, atypical BCR-ABL transcript, additional chromosomal aberrations, and evolving MDS is uncommon and therapeutically challenging. The prognostic significance of these genetic findings is uncertain, even as singular aberrations, with nearly no data on management and outcome when they coexist. MDS evolving during the course of CML may be either treatment-associated or an independently coexisting disease, and is generally considered to have an inferior prognosis. Tyrosine kinase inhibitors (TKI) directed against BCR-ABL are the mainstay of treatment for CML, whereas treatment modalities that may be utilized for MDS and CML include allogeneic stem cell transplant and – at least conceptually – hypomethylating agents.
Case report: Here, we describe the clinical course of such a patient, demonstrating that long-term combined treatment with dasatinib and azacitidine for coexisting CML and MDS is feasible and well tolerated, and may be capable of slowing disease progression. This combination therapy had no deleterious effect on subsequent potentially curative haploidentical bone marrow transplantation.
Conclusions: The different prognostic implications of this unusual case and new therapeutic options in CML are discussed, together with a review of the current literature on CML presenting with different types of genomic aberrations and the coincident development of MDS. Additionally, this case gives an example of long-term combined treatment of tyrosine kinase inhibitors and hypomethylating agents, which could be pioneering in CML treatment.
Cellular attachment plays a vital role in the differentiation of pheochromocytoma (PC12) cells. PC12 cells are noradrenergic clonal cells isolated from the adrenal medulla of Rattus norvegicus and studied extensively as they have the ability to differentiate into sympathetic neuron-like cells. The effect of several experimental parameters including (i) the concentration of nerve growth factor (NGF); (ii) substratum coatings, such as poly-L-lysine (PLL), fibronectin (Fn), and laminin (Lam); and (iii) double coatings composed of PLL/Lam and PLL/Fn on the differentiation process of PC12 cells were studied. Cell morphology was visualised using brightfield phase contrast microscopy, cellular metabolism and proliferation were quantified using a 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay, and the neurite outgrowth and axonal generation of the PC12 cells were evaluated using wide field fluorescence microscopy. It was found that double coatings of PLL/Lam and PLL/Fn supported robust adhesion and a two-fold enhanced neurite outgrowth of PC12 cells when treated with 100 ng/mL of NGF while exhibiting stable metabolic activity, leading to the accelerated generation of axons.
We present a dataset of free-viewing eye-movement recordings that contains more than 2.7 million fixation locations from 949 observers on more than 1000 images from different categories. This dataset aggregates and harmonizes data from 23 different studies conducted at the Institute of Cognitive Science at Osnabrück University and the University Medical Center in Hamburg-Eppendorf. Trained personnel recorded all studies under standard conditions with homogeneous equipment and parameter settings. All studies allowed for free eye-movements, and differed in the age range of participants (~7–80 years), stimulus sizes, stimulus modifications (phase scrambled, spatial filtering, mirrored), and stimuli categories (natural and urban scenes, web sites, fractal, pink-noise, and ambiguous artistic figures). The size and variability of viewing behavior within this dataset presents a strong opportunity for evaluating and comparing computational models of overt attention, and furthermore, for thoroughly quantifying strategies of viewing behavior. This also makes the dataset a good starting point for investigating whether viewing strategies change in patient groups.
Background: The Aedes (Stegomyia) albopictus subgroup includes 11 cryptic species of which Ae. albopictus is the most widely distributed. Its global expansion associated with a documented vector competence for several emerging arboviruses raise obvious concerns in the recently colonized regions. While several studies have provided important insights regarding medical importance of Ae. albopicus, the investigations of the other sibling species are scarce. In Asia, indigenous populations within the Ae. albopictus subgroup can be found in sympatry. In the present study, we aimed to describe and compare molecular, morphological and bacterial symbionts composition among sympatric individuals from the Ae. albopictus subgroup inhabiting a Vietnamese protected area.
Results: Based on morphological structure of the cibarial armarture, we identified a cryptic species in the forest park at Bù Gia Mập in the south-eastern region of Vietnam. Analysis of nuclear (ITS1-5.8S-ITS2) and mitochondrial (cox1, nad5) markers confirmed the divergence between the cryptic species and Ae. albopictus. Analysis of midgut bacterial microbiota revealed a strong similarity among the two species with a notable difference; contrary to Ae. albopictus, the cryptic species did not harbour any Wolbachia infection.
Conclusions: These results could reflect either a recent invasion of Wolbachia in Ae. albopictus or alternatively a loss of this symbiont in the cryptic species. We argue that neglected species of the Ae. albopictus subgroup are of main importance in order to estimate variation of host-symbionts interactions across evolution.
Ion channel gating is essential for cellular homeostasis and is tightly controlled. In some eukaryotic and most bacterial ligand-gated K+ channels, RCK domains regulate ion fluxes. Until now, a single regulatory mechanism has been proposed for all RCK-regulated channels, involving signal transduction from the RCK domain to the gating area. Here, we present an inactive ADP-bound structure of KtrAB from Vibrio alginolyticus, determined by cryo-electron microscopy, which, combined with EPR spectroscopy and molecular dynamics simulations, uncovers a novel regulatory mechanism for ligand-induced action at a distance. Exchange of activating ATP to inactivating ADP triggers short helical segments in the K+-translocating KtrB dimer to organize into two long helices that penetrate deeply into the regulatory RCK domains, thus connecting nucleotide-binding sites and ion gates. As KtrAB and its homolog TrkAH have been implicated as bacterial pathogenicity factors, the discovery of this functionally relevant inactive conformation may advance structure-guided drug development.
SR proteins function in nuclear pre-mRNA processing, mRNA export, and translation. To investigate their cellular dynamics, we developed a quantitative assay, which detects differences in nucleocytoplasmic shuttling among seven canonical SR protein family members. As expected, SRSF2 and SRSF5 shuttle poorly in HeLa cells but surprisingly display considerable shuttling in pluripotent murine P19 cells. Combining individual-resolution cross-linking and immunoprecipitation (iCLIP) and mass spectrometry, we show that elevated arginine methylation of SRSF5 and lower phosphorylation levels of cobound SRSF2 enhance shuttling of SRSF5 in P19 cells by modulating protein-protein and protein-RNA interactions. Moreover, SRSF5 is bound to pluripotency-specific transcripts such as Lin28a and Pou5f1/Oct4 in the cytoplasm. SRSF5 depletion reduces and overexpression increases their cytoplasmic mRNA levels, suggesting that enhanced mRNA export by SRSF5 is required for the expression of pluripotency factors. Remarkably, neural differentiation of P19 cells leads to dramatically reduced SRSF5 shuttling. Our findings indicate that posttranslational modification of SR proteins underlies the regulation of their mRNA export activities and distinguishes pluripotent from differentiated cells.