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Background: In cystic fibrosis, highly variable glucose tolerance is suspected. However, no study provided within-patient coefficients of variation. The main objective of this short report was to evaluate within-patient variability of oral glucose tolerance.
Methods: In total, 4,643 standardized oral glucose tolerance tests of 1,128 cystic fibrosis patients (median age at first test: 15.5 [11.5; 21.5] years, 48.8% females) were studied. Patients included were clinically stable, non-pregnant, and had at least two oral glucose tolerance tests, with no prior lung transplantation or systemic steroid therapy. Transition frequency from any one test to the subsequent test was analyzed and within-patient coefficients of variation were calculated for fasting and two hour blood glucose values. All statistical analysis was implemented with SAS 9.4.
Results: A diabetic glucose tolerance was confirmed in 41.2% by the subsequent test. A regression to normal glucose tolerance at the subsequent test was observed in 21.7% and to impaired fasting glucose, impaired glucose tolerance or both in 15.2%, 12.0% or 9.9%. The average within-patient coefficient of variation for fasting blood glucose was 11.1% and for two hour blood glucose 25.3%.
Conclusion: In the cystic fibrosis patients studied, a highly variable glucose tolerance was observed. Compared to the general population, variability of two hour blood glucose was 1.5 to 1.8-fold higher.
The approximate number system (ANS) has been consistently found to be associated with math achievement. However, little is known about the interactions between the different instantiations of the ANS and in how many ways they are related to exact calculation. In a cross-sectional design, we investigated the relationship between three measures of ANS acuity (non-symbolic comparison, non-symbolic estimation and non-symbolic addition), their cross-sectional trajectories and specific contributions to exact calculation. Children with mathematical difficulties (MD) and typically achieving (TA) controls attending the first six years of formal schooling participated in the study. The MD group exhibited impairments in multiple instantiations of the ANS compared to their TA peers. The ANS acuity measured by all three tasks positively correlated with age in TA children, while no correlation was found between non-symbolic comparison and age in the MD group. The measures of ANS acuity significantly correlated with each other, reflecting at least in part a common numerosity code. Crucially, we found that non-symbolic estimation partially and non-symbolic addition fully mediated the effects of non-symbolic comparison in exact calculation.
Introduction: Curare is one of the best-examined neurotoxins of the world, which has empirically been used for centuries by American Indigenes. Research on curare has been performed much later, a global scientometric analysis on curare research or its derivates does not yet exist. This bibliometric analysis is part of the global NewQis-project and should illuminate both toxic and historic issues of research on curare.
Methods: The ISI Web of Science was searched for data covering 1900 to 2013 using a term which included as many original articles on curare as possible. 3,867 articles were found and analyzed for common bibliometric items such as the number of citations, language of the articles or the (modified) Hirsch-Index (h-index). Results are illustrated utilizing modern density equalizing map projections (DEMP) or beam diagrams.
Results: Most publications were located in North America and Europe. The USA has the highest number of publications as well as the highest h-index. The number of publications overall rose until the late 1990s and later decreased. Furthermore, sudden increases of research activity are ascribable to historic events, like the first use of curare as muscle relaxant during surgery.
Discussion: This scientometric analysis of curare research reflects several tendencies as previously seen in other bibliometric investigations, i.e. the scientific quality standard of North America and Europe. Research on curare decreased however, due to the declining attention towards this muscle relaxant. This work exemplifies also how scientometric methods can be used to illuminate historic circumstances immediately stimulating scientific research.
Introduction: To determine the esthetic outcome of implant-based reconstructions after autologous and allogeneic bone grafting.
Methods: From 2003 to 2009, 67 patients underwent alveolar ridge augmentation and were enrolled in the study, 41 meet the inclusion criteria and 31 agreed to take part in the study. Patients were 18-69 years old (mean: 49.3 ± 13.8 years), and predominantly female. Patients received bone block grafts either autologous (n = 48) (AUBB) or allografts (ABB) (n = 19). Implants were inserted 4-7 months (autografts) or 5-6 months (allografts) after bone grafting. The Pink Esthetic Score (PES) as well as radiographic and subjective assessments were employed for the outcome analysis. The PES was assessed twice within one month based on digital photographic images that were randomly rearranged between evaluations by three independent, experienced investigators.
Results: Across all observations and investigators, the average PES was 7.5 ± 2.6 without differences between implants inserted in auto- and allografted bone, respectively. Patients assessed the allograft procedures as less painful and would have repeated it more often. The intra-rater reliability was excellent (correlation coefficients 0.7-0.9). The inter-observer agreement was lower (correlation coefficients 0.6-0.8).
Conclusions: Bone grafting with ABB allografts yields equivalent results to autologous grafting, and patients appreciate the omission of bone harvesting. The PES is a reliable method but should be performed by the same individual.
In this study, we describe the synthesis of 1,4-disustituted-1,2,3-triazolo-quinazoline ribonucleosides or acyclonucleosides by means of 1,3-dipolar cycloaddition between various O or N-alkylated propargyl-quinazoline and 1'-azido-2',3',5'-tri-O-benzoylribose or activated alkylating agents under microwave conditions. None of the compounds selected showed significant anti-HCV activity in vitro.
Recent advances in understanding the mechanisms of nonsmall cell lung cancer (NSCLC) has led to the development of targeted treatments, including the reversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors gefitinib and erlotinib, and the irreversible ErbB family blocker afatinib. Several important activating EGFR mutations have now been identified, which correlate strongly with response to treatment with these agents. Multiple randomised controlled trials have confirmed the association between the presence of activating EGFR mutations and objective response to gefitinib, erlotinib and afatinib, thus demonstrating their superiority over platinum-based chemotherapy as first-line treatment for NSCLC patients with EGFR mutation-positive tumours, and resulting in approval of these agents for use in this setting. It can be tempting to compare outcome data across multiple clinical trials and agents; however, substantial differences in methodology between studies, including investigator versus independent assessment and differences in patient eligibility, makes such comparisons fraught with difficulty. This critical review provides an overview of the evolution of the methodology used in eight phase III trials investigating first-line targeted treatment of NSCLC, identifies key differences in methodology and reporting, and critically assesses how these differences should be taken into account when interpreting the findings from such trials.
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare haematopoietic malignancy characterized by dismal prognosis and overall poor therapeutic response. Since the biology of BPDCN is barely understood, our study aims to shed light on the genetic make-up of these highly malignant tumors. Using targeted high-coverage massive parallel sequencing, we investigated 50 common cancer genes in 33 BPDCN samples. We detected point mutations in NRAS (27.3% of cases), ATM (21.2%), MET, KRAS, IDH2, KIT (9.1% each), APC and RB1 (6.1% each), as well as in VHL, BRAF, MLH1, TP53 and RET (3% each). Moreover, NRAS, KRAS and ATM mutations were found to be mutually exclusive and we observed recurrent mutations in NRAS, IDH2, APC and ATM. CDKN2A deletions were detected in 27.3% of the cases followed by deletions of RB1 (9.1%), PTEN and TP53 (3% each). The mutual exclusive distribution of some mutations may point to different subgroups of BPDCN whose biological significance remains to be explored.
1D-3D hybrid modeling : from multi-compartment models to full resolution models in space and time
(2014)
Investigation of cellular and network dynamics in the brain by means of modeling and simulation has evolved into a highly interdisciplinary field, that uses sophisticated modeling and simulation approaches to understand distinct areas of brain function. Depending on the underlying complexity, these models vary in their level of detail, in order to cope with the attached computational cost. Hence for large network simulations, single neurons are typically reduced to time-dependent signal processors, dismissing the spatial aspect of each cell. For single cell or networks with relatively small numbers of neurons, general purpose simulators allow for space and time-dependent simulations of electrical signal processing, based on the cable equation theory. An emerging field in Computational Neuroscience encompasses a new level of detail by incorporating the full three-dimensional morphology of cells and organelles into three-dimensional, space and time-dependent, simulations. While every approach has its advantages and limitations, such as computational cost, integrated and methods-spanning simulation approaches, depending on the network size could establish new ways to investigate the brain. In this paper we present a hybrid simulation approach, that makes use of reduced 1D-models using e.g., the NEURON simulator—which couples to fully resolved models for simulating cellular and sub-cellular dynamics, including the detailed three-dimensional morphology of neurons and organelles. In order to couple 1D- and 3D-simulations, we present a geometry-, membrane potential- and intracellular concentration mapping framework, with which graph- based morphologies, e.g., in the swc- or hoc-format, are mapped to full surface and volume representations of the neuron and computational data from 1D-simulations can be used as boundary conditions for full 3D simulations and vice versa. Thus, established models and data, based on general purpose 1D-simulators, can be directly coupled to the emerging field of fully resolved, highly detailed 3D-modeling approaches. We present the developed general framework for 1D/3D hybrid modeling and apply it to investigate electrically active neurons and their intracellular spatio-temporal calcium dynamics.
Zur Bestandserfassung der Mauerflora und Mauervegetation in Herne, Bochum, Hattingen und Witten im mittleren und südlichen Ruhrgebiet wurden in den Jahren 2007 und 2008 insgesamt 68 Vegetationsaufnahmen nach Braun-Blanquet angefertigt. Ziel dieser Untersuchung war, nicht nur ein Bild von der Verbreitung und den Häufigkeiten einzelner Sippen zu gewinnen, sondern zu untersuchen, ob nicht auch typische Pflanzengesellschaften ausgebildet sind oder ob die Vergesellschaftung der aus anderen deutschen Städten bekannten, vielerorts häufigen und hinlänglich beschriebenen Mauergesellschaften im mittleren Ruhrgebiet möglicherweise nur unvollständig bzw. fragmentarisch ausgebildet ist. Ein besonderer Schwerpunkt der Untersuchungen lag dabei auf den Farnpflanzen und den von ihnen aufgebauten Pflanzengesellschaften. Die Ergebnisse werden in einen naturräumlichen, chorologischen, vegetationskundlichen und stadtökologischen Kontext gestellt. Des Weiteren werden bemerkenswerte Taxa, wie beispielsweise gefährdete und seltene Sippen, ausführlicher kommentiert.
Background: Birch pollen-allergic subjects produce polyclonal cross-reactive IgE antibodies that mediate pollen-associated food allergies. The major allergen Bet v 1 and its homologs in plant foods bind IgE in their native protein conformation. Information on location, number and clinical relevance of IgE epitopes is limited. We addressed the use of an allergen-related protein model to identify amino acids critical for IgE binding of PR-10 allergens.
Method: Norcoclaurine synthase (NCS) from meadow rue is structurally homologous to Bet v 1 but does not bind Bet v 1-reactive IgE. NCS was used as the template for epitope grafting. NCS variants were tested with sera from 70 birch pollen allergic subjects and with monoclonal antibody BV16 reported to compete with IgE binding to Bet v 1.
Results: We generated an NCS variant (Δ29NCSN57/I58E/D60N/V63P/D68K) harboring an IgE epitope of Bet v 1. Bet v 1-type protein folding of the NCS variant was evaluated by 1H-15N-HSQC NMR spectroscopy. BV16 bound the NCS variant and 71% (50/70 sera) of our study population showed significant IgE binding. We observed IgE and BV16 cross-reactivity to the epitope presented by the NCS variant in a subgroup of Bet v 1-related allergens. Moreover BV16 blocked IgE binding to the NCS variant. Antibody cross-reactivity depended on a defined orientation of amino acids within the Bet v 1-type conformation.
Conclusion: Our system allows the evaluation of patient-specific epitope profiles and will facilitate both the identification of clinically relevant epitopes as biomarkers and the monitoring of therapeutic outcomes to improve diagnosis, prognosis, and therapy of allergies caused by PR-10 proteins.
Background: Tracks of pigeons homing to the Frankfurt loft revealed an odd phenomenon: whereas birds returning from the North approach their loft more or less directly in a broad front, pigeons returning from the South choose, from 25 km from home onward, either of two corridors, a direct one and one with a considerable detour to the West. This implies differences in the navigational process.
Methodology/Principle Findings: Pigeons released at sites at the beginning of the westerly corridor and in this corridor behave just like pigeons returning from farther south, deviating to the west before turning towards their loft. Birds released at sites within the straight corridors, in contrast, take more or less straight routes. The analysis of the short-term correlation dimension, a quantity reflecting the complexity of the system and with it, the number of factors involved in the navigational process, reveals that it is significantly larger in pigeons choosing the westerly corridor than in the birds flying straight - 3.03 vs. 2.85. The difference is small, however, suggesting a different interpretation of the same factors, with some birds apparently preferring particular factors over others.
Conclusions: The specific regional distribution of the factors which pigeons use to determine their home course seems to provide ambiguous information in the area 25 km south of the loft, resulting in the two corridors. Pigeons appear to navigate by deriving their routes directly from the locally available navigational factors which they interpret in an individual way. The fractal nature of the correlation dimensions indicates that the navigation process of pigeons is chaotic-deterministic; published tracks of migratory birds suggest that this may apply to avian navigation in general.
Background: Highly infectious diseases (HIDs) are (i) easily transmissible from person to person; (ii) cause a life-threatening illness with no or few treatment options; and (iii) pose a threat for both personnel and the public. Hence, even suspected HID cases should be managed in specialised facilities minimizing infection risks but allowing state-of-the-art critical care. Consensus statements on the operational management of isolation facilities have been published recently. The study presented was set up to compare the operational management, resources, and technical equipment among European isolation facilities. Due to differences in geography, population density, and national response plans it was hypothesized that adherence to recommendations will vary.
Methods and Findings: Until mid of 2010 the European Network for Highly Infectious Diseases conducted a cross-sectional analysis of isolation facilities in Europe, recruiting 48 isolation facilities in 16 countries. Three checklists were disseminated, assessing 44 items and 148 specific questions. The median feedback rate for specific questions was 97.9% (n = 47/48) (range: n = 7/48 (14.6%) to n = 48/48 (100%). Although all facilities enrolled were nominated specialised facilities' serving countries or regions, their design, equipment and personnel management varied. Eighteen facilities fulfilled the definition of a High Level Isolation Unit'. In contrast, 24 facilities could not operate independently from their co-located hospital, and five could not ensure access to equipment essential for infection control. Data presented are not representative for the EU in general, as only 16/27 (59.3%) of all Member States agreed to participate. Another limitation of this study is the time elapsed between data collection and publication; e.g. in Germany one additional facility opened in the meantime.
Conclusion: There are disparities both within and between European countries regarding the design and equipment of isolation facilities. With regard to the International Health Regulations, terminology, capacities and equipment should be standardised.
Introduction: On-treatment HCV RNA measurements are crucial for the prediction of a sustained virological response (SVR) and to determine treatment futility during protease inhibitor-based triple therapies. In patients with advanced liver disease an accurate risk/benefit calculation based on reliable HCV RNA results can reduce the number of adverse events. However, the different available HCV RNA assays vary in their diagnostic performance.
Aim: To investigate the clinical relevance of concordant and discordant results of two HCV RNA assays during triple therapy with boceprevir and telaprevir in patients with advanced liver fibrosis/cirrhosis.
Methods: We collected on-treatment samples of 191 patients with advanced liver fibrosis/cirrhosis treated at four European centers for testing with the Abbott RealTime (ART) and COBAS AmpliPrep/COBAS TaqMan HCV v2.0 (CTM) assays.
Results: Discordant test results for HCV RNA detectability were observed in 23% at week 4, 17% at week 8/12 and 9% at week 24 on-treatment. The ART detected HCV RNA in 41% of week 4 samples tested negative by the CTM. However, the positive predictive value of an undetectable week 4 result for SVR was similar for both assays (80% and 82%). Discordance was also found for application of stopping rules. In 27% of patients who met stopping rules by CTM the ART measured levels below the respective cut-offs of 100 and 1000 IU/ml, respectively, which would have resulted in treatment continuation. In contrast, in nine patients with negative HCV RNA by CTM at week 24 treatment would have been discontinued due to detectable residual HCV RNA by the ART assay. Importantly, only 4 of these patients failed to achieve SVR.
Conclusion: Application of stopping rules determined in approval studies by one assay to other HCV RNA assays in clinical practice may lead to over and undertreatment in a significant number of patients undergoing protease inhibitor-based triple therapy.
Wassergefiltertes Infrarot A (wIRA) als spezielle Form der Wärmestrahlung mit hohem Eindringvermögen in das Gewebe bei geringer thermischer Oberflächenbelastung fördert die Heilung akuter und chronischer Wunden sowohl über thermische und temperaturabhängige als auch über nichtthermische und temperaturunabhängige Effekte. Wassergefiltertes Infrarot A steigert die Temperatur (+2,7°C in einer Gewebetiefe von 2 cm) und den Sauerstoffpartialdruck im Gewebe (+32% in einer Gewebetiefe von 2 cm) und die Gewebedurchblutung. Diese 3 Faktoren sind entscheidend für eine ausreichende Versorgung des Gewebes mit Energie und Sauerstoff und deshalb auch für Wundheilung und Infektionsabwehr. Wassergefiltertes Infrarot A hilft sowohl bei der normalen als auch bei der gestörten Wundheilung, indem es Entzündungsreaktionen und erhöhte Wundsekretion mindert, Infektionsabwehr und Regeneration fördert und Wundschmerzen lindern helfen kann. Die genannten Effekte wurden in insgesamt 7 prospektiven Studien (davon 6 randomisierten kontrollierten Studien) belegt, die meisten mit einem Evidenzgrad von Ia bzw. Ib. Die hier zusätzlich dargestellten Fallbeispiele komplizierter Wundheilungsverläufe illustrieren die belegten Wirkungen von wIRA. Nicht nur in den hier gezeigten 6 Fällen wendeten die Bestrahlungen mit wIRA komplizierte Wundheilungsverläufe zum Besseren und ermöglichten nach ganz unterschiedlich langen Gesamtdauern der Bestrahlungen (in den 6 Fällen: von 51–550 h) und nach verschieden langen Gesamtdauern der Wundpflege, meist nach Transplantation von Spalthautgittern, die Heilung der Wunden. Bei komplizierten Wundheilungsverläufen ersetzt wIRA nicht den Rat und ggf. auch die Behandlung eines erfahrenen plastischen Chirurgen und eines Chirurgen mit der Spezialisierung in septischer Chirurgie. Mit dieser Einschränkung kann wIRA als wertvolle Ergänzung der Behandlung von akuten und chronischen Wunden empfohlen werden.
A phytosociological survey of weed (segetal) vegetation in Slovakia was performed. A total of 508 relevés were sampled in 2002–2008. The aims of this study were to determine the actual distribution of the segetal communities, to analyze their floristic structure, and to evaluate their relationships to selected environmental factors. Thirteen plant communities of the class Stellarietea mediae were distinguished by cluster analysis; 11 communities were included in the subclass Violenea arvensis (Lathyro tuberosi-Adonidetum aestivalis, Consolido-Anthemidetum austriacae, Euphorbio exiguae-Melandrietum noctiflori, Veronicetum trilobae-triphyllidi, Lamio amplexicauli-Thlaspietum arvensis, Taraxacum sect. Ruderalia community, Spergulo arvensis-Scleranthetum annui, Myosotido-Sonchetum arvensis, Echinochloo-Setarietum pumilae, Galinsogo-Setarietum, and Stachyo annui-Setarietum pumilae) and two in the subclass Sisymbrienea (Portulacetum oleraceae and Setario viridis-Erigeronetum canadensis). Communities were characterized by diagnostic, constant, and dominant species and their structure, ecology, and distribution were estimated. The species composition of these communities was documented in synoptic and association tables. DCA ordination and analysis of variance was used to determine the main environmental factors of floristic differentiation and to determine ecological and structural differences among the communities. The analyses showed that the most important factors affecting floristic composition and classification of the weed communities are their time of development (agroecophase), the type of crops and altitude.
Bestände, die von Calamagrostis epigejos dominiert werden, gehören zu den charakteristischen Elementen der Vegetation im östlichen Mitteleuropa. In der Literatur wurden Calamagrostis epigejos-Gesellschaften bisher meist als monoton, artenarm und wenig divers beschrieben. Für den Berliner Raum wurden 54 Vegetationsaufnahmen von Brachflächen und ehemaligen Rieselfeldern ausgewertet, in denen C. epigejos dominant war (Deckung >25 %). Die C. epigejos-Dominanzbestände konnten hauptsächlich zwei Gesellschaften zugeordnet werden: der Calamagrostis epigejos-(Galio-Urticetea)-Gesellschaft und der Calamagrostis epigejos-(Onopordetalia/Agropyretalia)-Gesellschaft. Die Calamagrostis epigejos-(Galio-Urticetea)-Gesellschaft wächst auf nährstoffreichen, frischen bis nassen, zum Teil auch zeitweilig überstauten Flächen. Derartige Standortverhältnisse sind vor allem auf eutrophierten ehemaligen Rieselfeldern zu finden. Die Bestände der Calamagrostis epigejos-(Onopordetalia/Agropyretalia)-Gesellschaft kommen auf nährstoffärmeren und trockeneren Standorten vor. Für die mittleren F- und N-Zeigerwerte ergeben sich jeweils signifikante Unterschiede von 1,4 Stufen zwischen beiden Gesellschaften; für die mittleren R-Zeigerwerte beträgt der Unterschied 0,4 Stufen.
River corridor plants in Central Europe account for an above-average proportion of endangered species. The main objective of this study was to examine the effects of habitat fragmentation and abiotic conditions on the survival and changes in population size of four endangered, long-lived river corridor plant species (Euphorbia palustris, Pseudolysimachion longifolium, Sanguisorba officinalis, and Senecio paludosus) over the course of at least ten years. We sampled altogether 138 populations in the Weser and Elbe river systems in Northwestern Germany.
Overall, 33% of the populations went extinct during the study period. Extinction rates and changes in population size were related to initial population sizes, but not to population isolation and only marginally so to habitat quality. Large populations (> 100 individuals) had a much higher probability to survive or increase in size (to > 1000 individuals) than smaller populations. There was no general decline in population size in surviving populations, and extinction rates and changes in population size were independent of time. We therefore conclude that the high extinction rates in small populations are best explained by sudden short-term environmental events, such as changes in land use, rather than by long-term negative effects of, for example, genetic deterioration. A projection matrix for the next 117 years, however, predicted that 85% of the surveyed populations will have gone extinct. Since any establishment of new populations in the study area is unlikely owing to the lack of potential habitats and dispersal limitation, river corridor plants will probably continue to decline. Apart from preventing further habitat deterioration it will be crucial to maintain or establish an appropriate management, and to avoid sudden and adverse changes in land use.
Die vorliegende Arbeit liefert ein Kurzportrait von Botrychium simplex und beschreibt zunächst die biologischen Besonderheiten und die Verbreitung in Deutschland. In einem dritten Teil wird eine demographische Studie vorgestellt und über Langzeitbeobachtungen an der aktuell einzigen deutschen Population (in der Senne, Nordrhein-Westfalen) berichtet. Wie bei allen Mondrauten keimen bei B. simplex die Sporen im Boden, und die Gametophyten entwickeln sich nur weiter, wenn sie von einem arbuskulären Mykorrhizapilz infiziert wurden; auch die Sporophyten sind mykotroph. Typisch sind ein- oder auch mehrjährige Ruheperioden, in denen bei einzelnen Pflanzen keine oberirdischen Organe gebildet werden. Als kleinwüchsige und konkurrenzschwache Art ist B. simplex auf lückige und kurzrasige Pflanzengesellschaften angewiesen. Die morphologische Variabilität der Blätter ist ungewöhnlich groß, und vor allem die Form des sterilen Abschnitts ist vielgestaltig. Von den mehreren in Nordamerika unterschiedenen Varietäten kommt neben der häufigeren var. simplex auch var. tenebrosum in Mitteleuropa vor. Botrychium simplex ist eine Art der gemäßigten bis kühl-gemäßigten Zone mit einem Areal, das Europa, Nordamerika sowie Indien und Japan einschließt. In Deutschland sind Vorkommen aus 3 Jahrhunderten und auf 12 Messtischblättern belegt. Die Funde konzentrieren sich auf das 19. Jahrhundert; aus dem 20. Jahrhundert stammen lediglich 5 Angaben.
Wet meadows are transitional habitats between wetlands and dry-mesophilous grasslands; thus, they are vital in sustaining biodiversity as sources, stepping stones and green corridors of species dispersal. It is especially valid for inland alkali vegetation, where high landscapescale patchiness is typical and rapid shifts between vegetation types occur frequently. Solonetz meadows (Beckmannion eruciformis) are among the bestpreserved open habitats in Europe harbouring a unique flora including several endemics. Besides their importance, studies on the vegetation of solonetz meadows are scarce even though this knowledge would be vital for their effective conservation and management. Using own records and literature data, we provide a synthesis of the alliance Beckmannion eruciformis to characterise its associations floristically and ecologically in five regions along the river Tisza, East Hungary. We studied three associations of the alliance: (i) Agrostio stoloniferae-Alopecuretum pratensis, (ii) Agrostio stoloniferae-Beckmannietum eruciformis and (iii) Agrostio stoloniferae-Glycerietum pedicellatae. We found that solonetz meadow associations were separated along a moisture gradient with Agrostio stoloniferae-Alopecuretum pratensis at the drier end and Agrostio stoloniferae-Glycerietum pedicellateae at the wet end. This gradient was also justified by the distribution of the phytosociological groups. The proportion of species of Festuco-Brometea division was the highest in Agrostio stoloniferae-Alopecuretum pratensis, while the proportion of Cypero-Phragmitetea species was the highest in Agrostio stoloniferae-Glycerietum pedicellateae. Species of Puccinellio-Salicornetea had the highest proportion in Agrostio stoloniferae-Beckmannietum eruciformis, indicating the high soil salinity of this association. Our results suggest that Agrostio stoloniferae-Alopecuretum pratensis association plays an important role in preserving the continental flora elements of the surrounding dry grasslands. The ecological indicator values for soil moisture and salinity suggest that in case of the studied solonetz meadow associations, humidity increases with decreasing elevation, while salinity is highest at medium elevations. Our results suggest that Agrostio stoloniferae-Beckmannietum eruciformis is a transition towards salt marsh associations, while Agrostio stoloniferae-Glycerietum pedicellatae is a transition towards freshwater marshes. Our results show that preserving solonetz meadows is an important task for nature conservation as they have a crucial role in maintaining landscapescale species and habitat diversity and act as buffer zones around wetlands.
In Luxemburg sind infolge von Landnutzungsintensivierungen nur noch wenige Relikte nährstoffarmer Feuchthabitate mit hohem Naturschutzwert erhalten. Eine kleinräumig differenzierte Untersuchung der Zusammenhänge zwischen Bodenfaktoren und Vegetation stand für diese Relikte bisher aus. Aus diesem Grund wurden in fünf Luxemburger Niedermoorkomplexen Vegetationszusammensetzung, Vegetationsstruktur (90 %-Perzentil der Vegetationshöhe, Streudeckung) und für die Pflanzenernährung relevante, bodenchemische Variablen (pH-Wert, Phosphor-, Kalium-, Calcium-, Magnesium-Gehalt) erfasst sowie Ellenberg-Zeigerwerte (Feuchte- und Nährstoff-Zahl) ausgewertet. Dabei ging es insbesondere um die Klärung der Fragen, welche Umweltgradienten der auffälligen Zonierung in Kern- und Randbereiche zugrunde liegen und welche Habitateigenschaften mit der Anzahl von gefährdeten Arten korrelieren. Hierzu wurden insgesamt 74 Kleinflächen in den beiden Zonen angelegt und floristisch sowie bodenchemisch analysiert.
Die Kleinflächen spannten einen Säuregradienten von annähernd drei pH-Stufen über die Gebiete hinweg auf (pH 3,9–6,5). Es ließen sich floristische, strukturelle und bodenchemische Unterschiede zwischen den Zonen ausmachen. In den meisten Gebieten unterschieden sich Diversität (in Kernbereichen erhöht) und Produktivität (nach Maßgabe von 90 %-Perzentil und Nährstoff-Zahl in Randbereichen erhöht). Die bodenchemischen Variablen zeigten je nur in einzelnen Gebieten Zonenunterschiede. Die beiden Gebiete mit den niedrigsten bzw. höchsten pH-Werten wiesen die meisten Variablen mit signifikanten Zonenunterschieden auf. Die Feuchte-Zahl war in keinem Gebiet zonenkennzeichnend. Die Diversität an bedrohten Arten korrelierte am häufigsten mit dem Magnesiumgehalt im Boden (meist positiv) und dem 90 %-Perzentil (stets negativ).
Unsere Ergebnisse legen nahe, dass in den untersuchten Niedermoorkomplexen mehrere Variablen zugleich und in unterschiedlicher Kombination für die Zonation verantwortlich sein könnten. Es werden Managementoptionen für die gefährdeten Gebiete diskutiert.
Fluctuations of the water level at the edges of temporary water bodies provide favourable living conditions for annual plant communities of the phytosociological class Isoëto-Nanojuncetea. Such communities of periodically flooded ponds within the agricultural landscape of NE Germany are particularly rich in rare plant species of that class. During the past decades drainage, fertilisation and herbicides in the surrounding arable fields have led to a severe decline in diversity of these species. To develop efficient conservation strategies it is essential to understand the factors driving the species composition. Therefore, we studied how varying water regimes, soil properties and agricultural practices affect the diversity and species composition of these temporary ponds. The study was carried out in seven ponds on a conventionally managed farm in NE Brandenburg. At each of these wetlands mixed soil samples were taken to determine the pH, total nitrogen and phosphorus concentration. The plant species were recorded in 177 plots, each covering 1 x 1 m2. For each plot, the water level was recorded in April, July and August 2013, respectively, resulting in five "water level regimes". Total species number and percentages of Isoëto-Nanojuncetea species were determined per plot, to evaluate water level effects on the vegetation. In addition, mean Ellenberg indicator values for light, moisture and nutrients were calculated to assess the environmental conditions.
Large herbivores are significant vectors for the long distance dispersal of seeds in various habitats, both attached to animals (epizoochory) and via gut passage (endozoochory). The majority of studies on epizoochory have examined dispersal in the fur of domesticated ungulates. Studies on wild ungulates are important to understand dispersal processes in many habitats, but rare due to methodological constraints. We studied epizoochory of seeds by European bison in an open-forest-mosaic (nutrient poor grassland and heathland, mixed forest) in NW Germany, where bison had been introduced for the purpose of nature conservation. At the study site it was possible to apply a method by which hoof material of freeranging bison was non-invasively collected. We identified a total of 1082 seeds from 32 plant species in the hoof material. The three most abundant species were Polygonum aviculare, Agrostis capillaris and Betula spp. Seed species originated from various habitat types of the study area, while the majority of seeds derived from trampled areas. Compared to the non-dispersed plant species of the study area, dispersed plant species had a higher seed longevity index, suggesting that many seeds were picked up from the soil seed bank. Epizoochory ranking indices of dispersed seed species, classifying the importance of epizoochory, revealed that transport in the fur may be of minor importance for many species, i.e. epizoochory by the hooves turned out to be negatively correlated to epizoochory in the fur. We conclude that European bison disperses a considerable number of seed species through trampling. Further research should consider epizoochory via the hooves and include integrative approaches to understand the different dispersal mechanisms by ungulates and their longterm synergetic effect on plant communities.
Sekundärsukzession auf Kahlschlagflächen eines Buchenwaldes : Dauerflächenuntersuchungen 1971–2013
(2014)
Im Winter 1970/71 wurde durch den Göttinger Wald eine breite Schneise für ein neues Straßenbauprojekt geschlagen. Hier wurden im Sommer 1971 zwei Dauerflächen (F1, F2, je 8 x 8 m²) eingerichtet. Nachdem der Straßenbau aufgegeben wurde, konnten die Flächen mit ihrer natürlichen Sukzession bis heute kontinuierlich pflanzensoziologisch untersucht werden. Alljährlich wurden zweimal Vegetationsaufnahmen im Frühling und Sommer, vorwiegend mit Schätzung des Deckungsgrades der Schichten und Arten durchgeführt. Für die Auswertung über 43 Jahre wurden die Aufnahmedaten in Tabelle 1 und 2 als Beilage für jeweils mehrere Jahre mit Angaben von absoluter Stetigkeit und Deckungsgrad-Median zusammengefasst und mit einer aktuellen Aufnahme des benachbarten Buchenwaldes verglichen.
Ein im Jahr 2012 in Bayern verabschiedetes Naturwaldreservats-Forschungskonzept weist 26 der insgesamt 159 Reservate als Schwerpunktreservate für die künftige Dauerbeobachtung aus. 2013 wurden in vier der 26 Schwerpunktreservate erste Dauerbeobachtungsflächen eingerichtet. Alle Probeflächen liegen innerhalb von 1 ha großen Repräsentationsflächen der Schwerpunktreservate und umfassen jeweils 6 Probekreise mit einem Radius von 10 m (314 m2). Der Kreismittelpunkt wurde fest vermarkt; auf jedem der Probekreise wurde eine pflanzensoziologische Aufnahme nach Braun-Blanquet (1964) angefertigt.
Das Konzept des geplanten Langzeit-Monitorings der Waldbestände wird vorgestellt, Auswertungswege werden skizziert und an Hand der ersten in 2013 erhobenen Daten erläutert. Da die erhobenen Daten räumlich stark autokorreliert sind, wurden sie in einen für die Waldfläche Bayerns repräsentativen Referenzdatensatz eingehängt. Dieser besteht aus von Ewald (2009) für die pnV-Einstufung an 313 Probepunkten der nationalen Bodenzustandserhebung (BZE II) im 8 x 8 km Grundraster definierten Partneraufnahmen in den jeweils nächstgelegenen Naturwaldreservaten. Mittels Entzerrter Korrespondenzanalyse (DCA) wurden Aufnahme-Verteilungsmuster ermittelt. Der Referenzdatensatz ermöglichte eine objektive Waldgesellschafts-Zuordnung jeder Vegetationsaufnahme, indem die größte floristische Übereinstimmung zu einer Referenzaufnahme errechnet wurde. Die weitere Charakterisierung erfolgte anschließend über pflanzensoziologische Tabellenarbeit.
Die in je zwei Naturwaldreservaten im Hügelland Nord- und Südbayerns neu erhobenen Daten beinhalten Buchenwälder auf Kalk (Hordelymo-Fagetum) und Silikatstandorten (Galio- und Luzulo-Fagetum), Hangmischwälder (Adoxo-Aceretum) und Auwälder (Pruno-Fraxinetum, Querco-Ulmetum). Der vorherrschende Nährstoff- und Basengradient entspricht dem floristischen Hauptgefälle im gesamtbayerischen Referenzdatensatz. Ebenso wurde ein Gefälle von Wärmezeigern auf der 2. Achse in beiden Datensätzen (Referenzdatensatz und neu erhobene Daten) abgebildet. Im Falle der neu erhobenen Daten erscheint das Temperaturgefälle allerdings als Pseudo-Effekt, der durch Nadelholzanbau (mit-)verursacht ist. Die Möglichkeiten der Datenauswertung werden in den nächsten zwei Jahrzehnten sukzessive ansteigen. In dem bis 2022 vollständig erstinventarisierten Gesamtset der 26 Schwerpunkt-reservate wird künftig die Beobachtung der Dynamik innerhalb der Buchenwälder ebenso möglich sein wie im Randbereich sowie jenseits der Höhen-, Trocken- oder Nässegrenze der Buche.
Translation of mRNA into a polypeptide chain is a highly accurate process. Many prokaryotic and eukaryotic viruses, however, use leaky termination of translation to optimize their coding capacity. Although growing evidence indicates the occurrence of ribosomal readthrough also in higher organisms, a biological function for the resulting extended proteins has been elucidated only in very few cases. Here, we report that in human cells programmed stop codon readthrough is used to generate peroxisomal isoforms of cytosolic enzymes. We could show for NAD-dependent lactate dehydrogenase B (LDHB) and NAD-dependent malate dehydrogenase 1 (MDH1) that translational readthrough results in C-terminally extended protein variants containing a peroxisomal targeting signal 1 (PTS1). Efficient readthrough occurs at a short sequence motif consisting of a UGA termination codon followed by the dinucleotide CU. Leaky termination at this stop codon context was observed in fungi and mammals. Comparative genome analysis allowed us to identify further readthrough-derived peroxisomal isoforms of metabolic enzymes in diverse model organisms. Overall, our study highlights that a defined stop codon context can trigger efficient ribosomal readthrough to generate dually targeted protein isoforms. We speculate that beyond peroxisomal targeting stop codon readthrough may have also other important biological functions, which remain to be elucidated.
Dendritic morphology has been shown to have a dramatic impact on neuronal function. However, population features such as the inherent variability in dendritic morphology between cells belonging to the same neuronal type are often overlooked when studying computation in neural networks. While detailed models for morphology and electrophysiology exist for many types of single neurons, the role of detailed single cell morphology in the population has not been studied quantitatively or computationally. Here we use the structural context of the neural tissue in which dendritic trees exist to drive their generation in silico. We synthesize the entire population of dentate gyrus granule cells, the most numerous cell type in the hippocampus, by growing their dendritic trees within their characteristic dendritic fields bounded by the realistic structural context of (1) the granule cell layer that contains all somata and (2) the molecular layer that contains the dendritic forest. This process enables branching statistics to be linked to larger scale neuroanatomical features. We find large differences in dendritic total length and individual path length measures as a function of location in the dentate gyrus and of somatic depth in the granule cell layer. We also predict the number of unique granule cell dendrites invading a given volume in the molecular layer. This work enables the complete population-level study of morphological properties and provides a framework to develop complex and realistic neural network models.
Freshwater ecosystems are increasingly impacted by alien invasive species which have the potential to alter various ecological interactions like predator-prey and host-parasite relationships. Here, we simultaneously examined predator-prey interactions and parasitization patterns of the highly invasive round goby (Neogobius melanostomus) in the rivers Rhine and Main in Germany. A total of 350 N. melanostomus were sampled between June and October 2011. Gut content analysis revealed a broad prey spectrum, partly reflecting temporal and local differences in prey availability. For the major food type (amphipods), species compositions were determined. Amphipod fauna consisted entirely of non-native species and was dominated by Dikerogammarus villosus in the Main and Echinogammarus trichiatus in the Rhine. However, the availability of amphipod species in the field did not reflect their relative abundance in gut contents of N. melanostomus. Only two metazoan parasites, the nematode Raphidascaris acus and the acanthocephalan Pomphorhynchus sp., were isolated from N. melanostomus in all months, whereas unionid glochidia were only detected in June and October in fish from the Main. To analyse infection pathways, we examined 17,356 amphipods and found Pomphorhynchus sp. larvae only in D. villosus in the river Rhine at a prevalence of 0.15%. Dikerogammarus villosus represented the most important amphipod prey for N. melanostomus in both rivers but parasite intensities differed between rivers, suggesting that final hosts (large predatory fishes) may influence host-parasite dynamics of N. melanostomus in its introduced range.
Pseudoperonospora cubensis, an obligate biotrophic oomycete causing devastating foliar disease in species of the Cucurbitaceae family, was never reported in seeds or transmitted by seeds. We now show that P. cubensis occurs in fruits and seeds of downy mildew-infected plants but not in fruits or seeds of healthy plants. About 6.7% of the fruits collected during 2012–2014 have developed downy mildew when homogenized and inoculated onto detached leaves and 0.9% of the seeds collected developed downy mildew when grown to the seedling stage. This is the first report showing that P. cubensis has become seed-transmitted in cucurbits. Species-specific PCR assays showed that P. cubensis occurs in ovaries, fruit seed cavity and seed embryos of cucurbits. We propose that international trade of fruits or seeds of cucurbits might be associated with the recent global change in the population structure of P. cubensis.
Halophilic archaea cultivated from surface sterilized middle-late Eocene rock salt are polyploid
(2014)
Live bacteria and archaea have been isolated from several rock salt deposits of up to hundreds of millions of years of age from all around the world. A key factor affecting their longevity is the ability to keep their genomic DNA intact, for which efficient repair mechanisms are needed. Polyploid microbes are known to have an increased resistance towards mutations and DNA damage, and it has been suggested that microbes from deeply buried rock salt would carry several copies of their genomes. Here, cultivable halophilic microbes were isolated from a surface sterilized middle-late Eocene (38–41 million years ago) rock salt sample, drilled from the depth of 800 m at Yunying salt mine, China. Eight unique isolates were obtained, which represented two haloarchaeal genera, Halobacterium and Halolamina. We used real-time PCR to show that our isolates are polyploid, with genome copy numbers of 11–14 genomes per cell in exponential growth phase. The ploidy level was slightly downregulated in stationary growth phase, but the cells still had an average genome copy number of 6–8. The polyploidy of halophilic archaea living in ancient rock salt might be a factor explaining how these organisms are able to overcome the challenge of prolonged survival during their entombment.
Background: Emergency ultrasound is gaining importance in medical education. Widespread teaching methods are frontal presentations and hands-on training. The primary goal of our study was to evaluate the impact of frontal presentations (PS) by analysis of retained knowledge rate (RKR) and learning load (LL).
Methods: Our study was conducted during four introductory courses in emergency ultrasound covering Extended Focused Assessment with Sonography for Trauma (E-FAST) and Focused Echocardiography Evaluation in Life Support (FEEL). Standardized PS (length of 10 to 50 min) were presented by experienced trainers, who were asked to provide keywords, key messages, and images and assign a score to each. Group 1 consisted of 11 medical students with no prior ultrasound experience, and group 2 consisted of 80 physicians. Each group was audience to seven to eight standard PS and requested to answer a free text questionnaire after 0 h, 2.5 h, 24 h, and 14 days.
Results: In group 1, 168/176 questionnaires were analyzed, and 161/202 were analyzed in group 2. RKR in group 1 was 32.5%, 15%, 16%, and 12% at 0 h, 2.5 h, 24 h, and 2 weeks. The physicians' RKR were 23%, 20.5%, and 22.4% after 0, 2.5, and 24 h of a respective PS. The LL was 1.6/min for students and 1.2/min for physicians. There was no difference in RKR when comparing PS with higher and lower LL for both groups; shorter or case-based PS were associated with a higher RKR (p < 0.01).
Conclusions: Our study provides evidence that only a limited amount of information can be processed at a time. Only 12% of knowledge is retained after 2 weeks. Presentations of short duration can increase the retained knowledge rate. Therefore, frontal presentations and classroom-based ultrasound training and teaching should be adapted.
Background: Various kinase inhibitors are known to be ATP-binding cassette (ABC) transporter substrates and resistance acquisition to kinase inhibitors has been associated to increased ABC transporter expression. Here, we investigated the role of the ABC transporters ABCB1, ABCC1, and ABCG2 during melanoma cell resistance acquisition to the V600-mutant BRAF inhibitors PLX4032 (vemurafenib) and PLX4720. PLX4032 had previously been shown to interfere with ABCB1 and ABCG2. PLX4720 had been demonstrated to interact with ABCB1 but to a lower extent than PLX4032.
Findings: PLX4032 and PLX4720 affected ABCC1- and ABCG2-mediated drug transport in a similar fashion. In a panel of 16 V600E BRAF-mutated melanoma cell lines consisting of four parental cell lines and their sub-lines with acquired resistance to PLX4032, PLX4720, vincristine (cytotoxic ABCB1 and ABCC1 substrate), or mitoxantrone (cytotoxic ABCG2 substrate), we detected enhanced ABC transporter expression in 4/4 cytotoxic ABC transporter substrate-resistant, 3/4 PLX4720-resistant, and 1/4 PLX4032-resistant melanoma cell lines.
Conclusion: PLX4032 has the potential to induce ABC transporter expression but this potential is lower than that of PLX4720 or cytotoxic ABC transporter substrates. Since ABC transporters confer multi-drug resistance, this is of relevance for the design of next-line therapies.
Introduction: Over the last years, electronic cigarettes (ECs) have become more popular, particularly in individuals who want to give up smoking tobacco. The aim of the present study was to assess the influence of the different e-smoking liquids on the viability and proliferation of human periodontal ligament fibroblasts.
Method and materials: For this study six test solutions with components from ECs were selected: lime-, hazelnut- and menthol-flavored liquids, nicotine, propylene glycol, and PBS as control group. The fibroblasts were incubated up to 96 h with the different liquids, and cell viability was measured by using the PrestoBlue® reagent, the ATP detection and the migration assay. Fluorescence staining was carried out to visualize cell growth and morphology. Data were statistically analyzed by two-tailed one-way ANOVA.
Results: The cell viability assay showed that the proliferation rates of the cells incubated with nicotine or the various flavored liquids of the e-cigarettes were reduced in comparison to the controls, though not all reductions were statistically significant. After an incubation of 96 h with the menthol-flavored liquid the fibroblasts were statistically significant reduced (p < 0.001). Similar results were found for the detection of ATP in fibroblasts; the incubation with menthol-flavored liquids (p < 0.001) led to a statistically significant reduction. The cell visualization tests confirmed these findings.
Conclusion: Within its limits, the present in vitro study demonstrated that menthol additives of e-smoking have a harmful effect on human periodontal ligament fibroblasts. This might indicate that menthol additives should be avoided for e-cigarettes.
Background: Targeted therapies have improved therapeutic options of treating renal cell carcinoma (RCC). However, drug response is temporary due to resistance development.
Methods: Functional and molecular changes in RCC Caki-1 cells, after acquired resistance to the mammalian target of rapamycin (mTOR)-inhibitor everolimus (Cakires), were investigated with and without additional application of the histone deacetylase (HDAC)-inhibitor valproic acid (VPA). Cell growth was evaluated by MTT assay, cell cycle progression and apoptosis by flow cytometry. Target molecules of everolimus and VPA, apoptotic and cell cycle regulating proteins were investigated by western blotting. siRNA blockade was performed to evaluate the functional relevance of the proteins.
Results: Everolimus resistance was accompanied by significant increases in the percentage of G2/M-phase cells and in the IC50. Akt and p70S6K, targets of everolimus, were activated in Cakires compared to drug sensitive cells. The most prominent change in Cakires cells was an increase in the cell cycle activating proteins cdk2 and cyclin A. Knock-down of cdk2 and cyclin A caused significant growth inhibition in the Cakires cells. The HDAC-inhibitor, VPA, counteracted everolimus resistance in Cakires, evidenced by a significant decrease in tumor growth and cdk2/cyclin A.
Conclusion: It is concluded that non-response to everolimus is characterized by increased cdk2/cyclin A, driving RCC cells into the G2/M-phase. VPA hinders everolimus non-response by diminishing cdk2/cyclin A. Therefore, treatment with HDAC-inhibitors might be an option for patients with advanced renal cell carcinoma and acquired everolimus resistance.
Background: To report an unplanned interim analysis of a prospective, one-armed, single center phase I/II trial (NCT01566123).
Methods: Between 2007 and 2013, 27 patients (pts) with primary/recurrent retroperitoneal sarcomas (size > 5 cm, M0, at least marginally resectable) were enrolled. The protocol attempted neoadjuvant IMRT using an integrated boost with doses of 45-50 Gy to PTV and 50-56 Gy to GTV in 25 fractions, followed by surgery and IOERT (10-12 Gy). Primary endpoint was 5-year-LC, secondary endpoints included PFS, OS, resectability, and acute/late toxicity. The majority of patients showed high grade lesions (FNCLCC G1:18%, G2:52%, G3:30%), predominantly liposarcomas (70%). Median tumor size was 15 cm (6-31).
Results: Median follow-up was 33 months (5-75). Neoadjuvant IMRT was performed as planned (median dose 50 Gy, 26-55) in all except 2 pts (93%). Gross total resection was feasible in all except one patient. Final margin status was R0 in 6 (22%) and R1 in 20 pts (74%). Contiguous-organ resection was needed in all grossly resected patients. IOERT was performed in 23 pts (85%) with a median dose of 12 Gy (10-20 Gy).We observed 7 local recurrences, transferring into estimated 3- and 5-year-LC rates of 72%. Two were located outside the EBRT area and two were observed after more than 5 years. Locally recurrent situation had a significantly negative impact on local control. Distant failure was found in 8 pts, resulting in 3- and 5-year-DC rates of 63%. Patients with leiomyosarcoma had a significantly increased risk of distant failure. Estimated 3- and 5-year-rates were 40% for PFS and 74% for OS. Severe acute toxicity (grade 3) was present in 4 pts (15%). Severe postoperative complications were found in 9 pts (33%), of whom 2 finally died after multiple re-interventions. Severe late toxicity (grade 3) was scored in 6% of surviving patients after 1 year and none after 2 years.
Conclusion: Combination of neoadjuvant IMRT, surgery and IOERT is feasible with acceptable toxicity and yields good results in terms of LC and OS in patients with high-risk retroperitoneal sarcomas. Long term follow-up seems mandatory given the observation of late recurrences. Accrual of patients will be continued with extended follow-up.
Background: Evaluation of automated attenuation-based tube potential selection and its impact on image quality and radiation dose in CT (computed tomography) examinations for cancer staging.
Methods: A total of 110 (59 men, 51 women) patients underwent chest-abdomen-pelvis CT examinations; 55 using a fixed tube potential of 120 kV/current of 210 Reference mAs (using CareDose4D), and 55 using automated attenuation-based tube potential selection (CAREkV) also using a current of 210 Reference mAs. This evaluation was performed as a single-centre, observer-blinded retrospective analysis. Image quality was assessed by two readers in consensus. Attenuation, image noise, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were measured or calculated for objective image evaluation. For the evaluation of radiation exposure, dose-length-product (DLP) values were compared and Size-specific dose estimates (SSDE) values were calculated.
Results: Diagnostic image quality was obtained from all patients. The median DLP (703.5 mGy · cm, range 390–2203 mGy · cm) was 7.9% lower when using the algorithm compared with the standard 120 kV protocol (median 756 mGy · cm, range 345–2267 mGy · cm). A reduction in potential to 100 kV occurred in 32 cases; therefore, these patients received significantly lower radiation exposure compared with the 120 kV protocol.
Conclusion: Automated attenuation-based tube potential selection produces good diagnostic image quality in chest-abdomen-pelvis CT and reduces the patient’s overall radiation dose by 7.9% compared to the standard 120 kV protocol.
Rare copy-number variation (CNV) is an important source of risk for autism spectrum disorders (ASDs). We analyzed 2,446 ASD-affected families and confirmed an excess of genic deletions and duplications in affected versus control groups (1.41-fold, p = 1.0 × 10(-5)) and an increase in affected subjects carrying exonic pathogenic CNVs overlapping known loci associated with dominant or X-linked ASD and intellectual disability (odds ratio = 12.62, p = 2.7 × 10(-15), ∼3% of ASD subjects). Pathogenic CNVs, often showing variable expressivity, included rare de novo and inherited events at 36 loci, implicating ASD-associated genes (CHD2, HDAC4, and GDI1) previously linked to other neurodevelopmental disorders, as well as other genes such as SETD5, MIR137, and HDAC9. Consistent with hypothesized gender-specific modulators, females with ASD were more likely to have highly penetrant CNVs (p = 0.017) and were also overrepresented among subjects with fragile X syndrome protein targets (p = 0.02). Genes affected by de novo CNVs and/or loss-of-function single-nucleotide variants converged on networks related to neuronal signaling and development, synapse function, and chromatin regulation.
Background: According to current taxonomy only three out of 27 Sinohimalayan leaf warbler species (Phylloscopidae) are considered genetically uniform across their entire breeding range along the Southeastern margin of the Qinghai-Tibetan Plateau, the Buff-barred Warbler (Phylloscopus pulcher) being one of them. Because marked differentiation among Himalayan and Chinese populations has been recently demonstrated for a number of Phylloscopus species (or sister species) we investigated the intraspecific variation of a mitochondrial gene, songs and morphology of P. pulcher in a phylogeographic approach.
Methods: We sequenced a fragment of the mitochondrial cytochrome b, reconstructed haplotype networks and analyzed DNA polymorphism among Himalayan and Chinese populations. We measured time and frequency parameters of two distinct song types and analyzed among population-differentiation in a principal component analysis and a discriminant analysis. We also compared measurements of body size dimensions taken from museum specimens.
Results: The mitochondrial haplotype network (cytb) was divided into two distinct clusters corresponding to geographic origin of samples. Pairwise genetic distances among Himalayan and Chinese mtDNA lineages account for 1.3% which coincides with Pleistocene lineage separation at roughly 650,000 years ago. Genetic diversity is slightly higher in the Chinese part of the species’ range with respect to haplotype and nucleotide diversity while the less diversified Himalayan population lineage shows signs of recent range expansion. The vocal repertoire of P. pulcher comprises two distinct verse types that are combined with short interspersed click notes to long continuous song displays. Trill verse types showed significant differences among regions in almost all measured frequency and time parameters: Chinese males displayed more rapid and more broad-banded trills at a lower pitch. In contrast, warbling verse types showed a distinctively different structure among regions: Himalayan songs consisted of repeated syllables while Chinese songs comprised repetitions of single, long and strongly modulated elements. Subtle morphological differences among specimens from the two study regions could only be confirmed for plumage coloration but not for metric characters.
Conclusions: Based on the genetic and bioacoustic distinctiveness of Chinese Buff-barred Warbler populations, we recommend that the name Phylloscopus pulcher vegetus Bangs, 1913 should be re-validated for this taxon.
In diesem Beitrag werden an einigen Beispielen die Auswertungsmöglichkeiten aufgezeigt, die die digital vorliegende Vegetationskarte des Nationalparks Harz bietet. Es wird deutlich, dass beim Vergleich der vorliegenden Daten mit Wiederholungsaufnahmen Aussagen zu den ökologischen Veränderungen im Nationalpark Harz gemacht werden können, die das Ergebnis der natürlichen Sukzession bzw. das Ergebnis forstlicher Initialmaßnahmen sind. Die Arbeit zeigt, dass neben den Flächenanteilen der erfassten Pflanzengesellschaften die vorkommenden Arten und ihre Deckungsanteile in der jeweiligen Gesellschaft berechnet werden können. Damit ist es z. B. perspektivisch möglich, flächendeckende Aussagen zu den Ausbreitungstendenzen der Arten z. B. in den Pflanzengesellschaften und in den unterschiedlichen Höhenstufen des Nationalparks Harz zu machen. So zeigt die aktuelle Verbreitung von Picea abies im Nationalpark Harz, dass die Verteilung der Baumart nicht annähernd deckungsgleich mit der Verteilung ihrer natürlichen bzw. naturnahen Waldgesellschaften ist. Diese Diskrepanz tritt bei Fagus sylvatica nicht ganz so extrem auf. Am größten ist die Differenz in Höhenbereichen, in denen Fagus sylvatica ihr natürliches Verbreitungsgebiet hat, aber auch in der Vergangenheit am stärksten zurückgedrängt wurde. Das sind genau die Gebiete, in denen die Rotbuche im Rahmen der forstlichen Initialmaßnahmen des Nationalparks verstärkt eingebracht wurde. Ob Fagus sylvatica dort, wo sie gepflanzt wurde und in höheren Deckungsgraden auftritt, in der Lage ist, das Potenzial für natürliche Buchenwaldgesellschaften zu bilden, wird mit Hilfe der hier dargestellten Erfassungsmethode perspektivisch nachweisbar sein. Dass es sinnvoll ist, zu dem jetzigen Zeitpunkt zwischen naturnahen Waldgesellschaften und Fichtenforsten zu unterscheiden, wird anhand des Vergleichs ausgewählter Parameter aufgezeigt.
Herbaceous ground vegetation is an important pool of biomass and nutrients, which is also used as the major forage source for wild ungulates. Up to now no standard methods exist to estimate herbaceous biomass on a landscape level for temperate forests, which are characterised by deciduous trees with closed canopies. Quantity and quality of the herbaceous forage accessible to herbivores can be estimated from estimated cover in vegetation plot data and information on biomass and element concentrations in plant species. Vegetation was sampled stratified by community types and forest developmental phases in Bavarian Forst National Park, Germany. We adopted the PhytoCalc model to estimate biomass and bioelement stocks from vegetation plot data and adjusted species assignments and absolute levels of biomass to the conditions in the national park. We categorised attractiveness of plant species as forage for red deer (Cervus elaphus) and roe deer (Capreolus capreolus). Multiple controls of total biomass and of plant groups (graminoids, ferns, herbs, Vaccinium, Rubus) were studied by stepwise regression against stand and environmental predictors. Herbaceous mass had a highly skewed distribution in the park, with 75% of plots having less than 231 g*m-2 of biomass or 24 g*m-2 of raw protein. Contributions of plant groups were site-dependent and variable, but decreased in the order Vaccinium-graminoids-Rubus-herbs-ferns. Biomass appeared to be controlled by deciduous tree cover, by total cover of canopy and coarse woody debris and by site quality, with nutrient-poor, high elevation sites having higher herb biomass. As a consequence, montane beech forests offered less forage mass than coniferous communities of high elevations and mires. Stand disturbances by bark beetles and the corresponding forest developmental phases had no systematic effects on total biomass.
In den Bergwäldern der Bayerischen Alpen sind Standorte mit geringer Nachlieferung von N, P und K, z. T. auch von Mg und Ca weit verbreitet. Um diese gegenüber Biomassenutzung empfindlichen Standorte im Gelände zu erkennen, können Pflanzenarten der Bodenvegetation als Indikatoren genutzt werden. Ziel unserer Arbeit war es, anhand einer umfangreichen Vegetations- und Bodendatenbank Indikatorarten für nährstoffarme Waldstandorte in den Bayerischen Alpen zu ermitteln. Mit Hilfe einer Indikatorartenanalyse wurden insgesamt 745 verschiedene Gefäßpflanzenarten und die Torfmoose (auf Gattungsebene zusammengefasst) auf ihre Eignung als Indikatorarten überprüft. Dazu wurden insgesamt 1.496 durch Vegetationsaufnahmen und Bodenprofilansprachen gekennzeichnete Waldstandorte hinsichtlich ihrer Nährstoffversorgung eingestuft und ausgewertet. Potentilla erecta, Vaccinium vitis-idaea, Homogyne alpina und Huperzia selago wurden als allgemeine Indikatorarten für nährstoffarme Standorte ermittelt. Vorkommen von Vaccinium myrtillus (Deckung ≥ 5 %) sowie Vorkommen von Juncus effusus, Luzula sylvatica und Luzula pilosa weisen auf nährstoffarme, tiefgründig versauerte Mineralböden mit Auflagehumus hin, während Calamagrostis varia, Sesleria albicans, Melampyrum sylvaticum, Aster bellidiastrum und Anthoxanthum odoratum eng an nährstoffarme kalkreiche Standorte gebunden sind. Die dargestellten Indikatorarten wurden speziell für die nährstoffarmen Waldstandorte der Bayerischen Alpen zusammengestellt. Sie ermöglichen ohne viel Sach- und Zeitaufwand im Gelände eine Ansprache von nährstoffarmen Waldstandorten, deren Nährstoffangebot aus Standortskarten nur grob eingeschätzt werden kann.
Ziel: Die Vegetation der mitteleuropäischen Buchenwälder hat sich in den vergangenen Jahrzehnten deutlich verändert. Über die Änderungen in den wärmeliebenden Seggen-Hangbuchenwäldern (Carici-Fagetum) unter dem Einfluss des Nutzungs- und Klimawandels, der Eutrophierung und des Schalenwild-Einflusses ist aber bisher wenig bekannt. Wir verglichen Vegetationsaufnahmen des Carici-Fagetum aus den 1950er Jahren mit aktuellen und fragten: (1) Wie haben sich Struktur, Diversität und Artenzusammensetzung verändert? (2) Was sind die treibenden Faktoren dieser Veränderungen? (3) Welche Rückschlüsse ergeben sich für die zukünftige Entwicklung und Behandlung dieser Wälder?
Untersuchungsgebiet: Göttinger Wald (Süd-Niedersachsen, Deutschland, Mitteleuropa)
Methoden: Die Vegetation von 78 Quasi-Dauerflächen in vier Subassoziationen des Carici-Fagetum wurde im Zeitraum 1955 bis 1960 und 2011 bis 2012 aufgenommen. Unterschiede in der Vegetationsstruktur, der Diversität und Artenzusammensetzung sowie hinsichtlich verschiedener forstlicher und standortökologischer Parameter und ökologischer Artengruppen zwischen beiden Aufnahmeterminen wurden mit Hilfe von Ordinations- und Permutations-Verfahren sowie paarweiser Vergleiche analysiert und statistisch geprüft.
Ergebnisse: Strukturell hat vor allem die Strauchschicht stark zugenommen, insbesondere bedingt durch eine Intensivierung der Rehwild-Bejagung. In der Bodenvegetation haben die typischen Arten des Carici-Fagetum stark abgenommen, darunter auch viele Rote-Liste-Arten. Zugenommen haben dagegen neben den Gehölzen die weit verbreiteten Arten der mesophilen Buchenwälder. Dies zeigt sich auch in den Veränderungen der Zeigerwerte nach Ellenberg. Dem Rückgang von lichtliebenden, trockenheitsertragenden Magerkeitszeigern steht eine Zunahme von schattentoleranten, mesophilen und an eine bessere Nährstoffversorgung gebundenen Arten der geschlossenen Buchenwälder gegenüber, was zu einer zunehmenden Homogenisierung der Vegetation führt. Ursachen für diese Veränderungen sind das geänderte Bestandesklima durch eine dichter schließende Strauchschicht und atmosphärische Stickstoffeinträge, wobei letzteres wohl vor allem das Wachstum der Buche förderte. Eine deutliche Zunahme des immergrünen, ozeanisch verbreiteten Efeu (Hedera helix), der sehr empfindlich auf tiefe Temperaturen im Winter reagiert, gleichzeitig aber bei erhöhtem CO2-Angebot seine Wuchsleistung über proportional erhöht, kann als Reaktion auf den Klimawandel der letzten 50 Jahre gewertet werden. Positiv hat sich auch eine Reduktion des Rehwild-Verbisses auf diese und andere Arten – z. B. Lilium martagon als einzige Rote-Liste-Art mit einer positiven Deckungsgradentwicklung – ausgewirkt.
Schlussfolgerungen: Die wärmeliebenden Seggen-Hangbuchenwälder haben in den letzten 50 Jahren charakteristische und wertvolle floristische Elemente – häufig Relikte der früheren Mittelwaldnutzung in Verbindung mit Waldweide – verloren. Mit der Einstellung der forstlichen Nutzung, z. T. bedingt durch Naturschutzmaßnahmen, der Reduktion des Schalenwildverbisses und den atmosphärischen Nährstoffeinträgen zeigt das Carici-Fagetum im Göttinger Wald heute eine Sukzession zum mesophilen Wald, wie sie für viele thermophile Laubwälder in Mitteleuropa nach Jahrhunderten der Auflichtung und Aushagerung typisch geworden ist.
Background: Unlike metastatic colorectal cancer (CRC) there are to date few reports concerning the predictive value of molecular biomarkers on the clinical outcome in stage II/III CRC patients receiving adjuvant chemotherapy. Aim of this study was to assess the predictive value of proteins related with the EGFR- and VEGFR- signalling cascades in these patients.
Methods: The patients' data examined in this study were from the collective of the 5-FU/FA versus 5-FU/FA/irinotecan phase III FOGT-4 trial. Tumor tissues were stained by immunohistochemistry for VEGF-C, VEGF-D, VEGFR-3, Hif-1 α, PTEN, AREG and EREG expression and evaluated by two independent, blinded investigators. Survival analyses were calculated for all patients receiving adjuvant chemotherapy in relation to expression of all makers above.
Results: Patients with negative AREG and EREG expression on their tumor had a significant longer DFS in comparison to AREG/EREG positive ones (p< 0.05). The benefit on DFS in AREG-/EREG- patients was even stronger in the group that received 5-FU/FA/irinotecan as adjuvant treatment (p=0.002). Patients with strong expression of PTEN profited more in terms of OS under adjuvant treatment containing irinotecan (p< 0.05). Regarding markers of the VEGFR- pathway we found no correlation of VEGF-C- and VEGFR-3 expression with clinical outcome. Patients with negative VEGF-D expression had a trend to live longer when treated with 5-FU/FA (p=0.106). Patients who were negative for Hif-1 α, were disease-free in more than 50% at the end of the study and showed significant longer DFS-rates than those positive for Hif-1 α (p=0.007). This benefit was even stronger at the group treated with 5-FU/FA/irinotecan (p=0.026). Finally, AREG-/EREG-/PTEN+ patients showed a trend to live longer under combined treatment combination.
Conclusions: The addition of irinotecan to adjuvant treatment with 5-FU/FA does not provide OS or DFS benefit in patients with stage II/III CRC. Nevertheless, AREG/EREG negative, PTEN positive and Hif-1 α negative patients might profit significantly in terms of DFS from a treatment containing fluoropyrimidines and irinotecan. Our results suggest a predictive value of these biomarkers concerning adjuvant chemotherapy with 5-FU/FA +/− irinotecan in stage II/III colorectal cancer.
Background: Fatigue is a common symptom of chronic hepatitis C virus (HCV) infection and a frequent side-effect of peginterferon/ribavirin (PR) therapy for HCV. This study evaluated the impact of adding the oral HCV NS3/4A protease inhibitor simeprevir to PR on patient-reported fatigue and health status among patients with chronic HCV genotype 1 infection enrolled in the Phase IIb PILLAR and ASPIRE trials [NCT00882908; NCT00980330].
Methods: Treatment-naïve patients (PILLAR, n = 386) and treatment-experienced patients (ASPIRE, n = 462) were randomized to simeprevir plus PR (simeprevir/PR) or placebo plus PR (placebo/PR). In PILLAR, duration of PR treatment in the simeprevir/PR groups was determined using response-guided therapy (RGT) criteria. PR could be terminated at Week 24, instead of Week 48, if HCV RNA was <25 IU/mL by Week 4 and then undetectable at Weeks 12, 16, and 20. In both studies, patients completed the Fatigue Severity Scale (FSS) and EQ-5D quality-of-life questionnaire in their native language at baseline and throughout the studies up until Week 72.
Results: During the first 24 weeks of treatment, mean FSS total score was increased to a similar degree compared with baseline among patients receiving simeprevir/PR or placebo/PR in both studies indicating increased fatigue severity. Mean FSS scores returned to values comparable with baseline among patients receiving simeprevir/PR after Week 24 in PILLAR (after treatment completion for the majority of patients) and in ASPIRE (after Week 48), consistent with RGT enabling early termination of all treatment at Week 24 in 82.2% of simeprevir/PR-treated patients in the PILLAR study. Similar results were observed for EQ-5D, with simeprevir/PR-treated patients experiencing less time with worse health problems according to EQ-5D scores compared with placebo/PR groups in both studies, and more rapid improvement in health status associated with shorter treatment duration in the PILLAR study.
Conclusions: Combination of simeprevir with PR did not increase patient-reported fatigue severity or health status impairments beyond that reported by patients treated with PR alone. Many patients treated with simeprevir/PR returned to pretreatment fatigue and health status levels sooner due to increased treatment efficacy that enabled shorter duration of all therapy, compared with PR alone.
Background: Aviscumine, a recombinant plant protein, is an immune modulator that induces ribotoxic stress at the 28S ribosomal RNA subunit. In this way cytokine release and T-cell responses are enhanced. This phase II trial was conducted to test the efficacy and safety of aviscumine in patients with systemically pre-treated metastatic melanoma stage IV.
Methods: A total of 32 patients with progressive stage IV melanoma after failure of standard therapy were enrolled onto a single-arm, multi-centre, open-label, phase II trial. All patients had an ECOG performance status of 0 or 1. Patients received 350 ng aviscumine twice weekly by subcutaneous injection until progression. The primary end points were progression-free survival (PFS) and overall survival (OS). Safety was assessed as adverse events (AEs). Tumor response was assessed every eight weeks and survival of patients was followed up to one year after the end of therapy. Thirty one patients (intent-to-treat population (ITT)) were assessed for efficacy; safety was assessed in the whole population.
Results: One patient achieved a partial response (PR) and 10 patients showed stable disease/no change (SD). The median progression-free survival (mPFS) was 63 days (95% CI 57–85) and median overall survival (mOS) was 335 days (95% CI 210–604). In total 210 treatment-emergent adverse events were recorded. Grade 1 or 2 AEs occurred in 72% of patients and were mostly application-site effects such as pruritus Grade 3–4 treatment-emergent drug-related adverse events occurred in 9% of patients.
Conclusion: These results suggest that aviscumine may have a clinical impact in patients with previously treated metastatic melanoma and provide rationale for further clinical evaluation of this agent. In the light of effective new immune checkpoint blockers it might be a candidate for combinations with these agents.
Background: The federal state of Hesse, Germany, introduced a laboratory-based reporting scheme for carbapenem-resistant organisms (CROs).
Method: The results of the first year of mandated reporting of CROs from April 2012 through March 2013 to the Public Health Authority of Frankfurt/Main, responsible for a population of 700,000 inhabitants, are described.
Results: Within a period of 12 months 243 CROs were notified to the health authority. Of these 213 isolates had been reported from 16 of the 17 hospitals in Frankfurt/Main, 6 from ambulatory settings and 24 from clinics outside of Frankfurt/Main. Mean incidence rate per 1,000 patient days in hospitals was 0.138 (range 0.02-0.28).
Conclusion: In Frankfurt/Main almost all hospitals have reported CROs in the study period though the frequency of isolation varies strongly and many facilities only report CROs sporadically. Molecular data indicate a high diversity of different carbapenemases. Autochthonous transmission must be assumed despite the absence of major outbreaks. Rapid and coordinated efforts by clinicians and health departments are crucial to control the spread of CRO infections. The mandatory reporting scheme provides important data to guide the implementation of preventive measures.
Non-coding RNAs (ncRNAs) play various roles during central nervous system development. MicroRNAs (miRNAs) are a class of ncRNAs that exert their function together with argonaute proteins by post-transcriptional gene silencing of messenger RNAs (mRNAs). Several studies provide evidence for alterations in miRNA expression in patients with neurodegenerative diseases. Among these is huntington‘s disease (HD), a dominantly inherited fatal disorder characterized by deregulation of neuronal-specific mRNAs as well as miRNAs. Recently, next-generation sequencing (NGS) miRNA profiles from human HD and neurologically normal control brain tissues were reported. Five consistently upregulated miRNAs affect the expression of genes involved in neuronal differentiation, neurite outgrowth, cell death and survival. We re-analyzed the NGS data publicly available in array express and detected nineteen additional differentially expressed miRNAs. Subsequently, we connected these miRNAs to genes implicated in HD development and network analysis pointed to miRNA-mediated downregulation of twenty-two genes with roles in the pathogenesis as well as treatment of the disease. In silico prediction and reporter systems prove that levels of BDNF, a central node in the miRNA-mRNA regulatory network, can be post-transcriptionally controlled by upregulated miR-10b-5p and miR-30a-5p. Reduced BDNF expression is associated with neuronal dysfunction and death in HD. Moreover, the 3’UTR of CREB1 harbors a predicted binding site for these two miRNAs. CREB1 is similarly downregulated in HD and overexpression decreased susceptibility to 3-nitropropionic-induced toxicity in a cell model. In contradiction to these observations, it is presumed that miR-10b-5p upregulation in HD exerts a neuroprotective role in response to the mutation in the huntingtin gene. Therefore, the function of miR-10b-5p and especially its effect on BDNF expression in HD requires further academic research.
(Micro)plastics in the aquatic environment are an issue of emerging concern. However, to date, there is considerable lack of knowledge on the abundance and toxicity of plastic debris in aquatic ecosystems, especially with regard to the freshwater situation. In this editorial, we briefly discuss important aspects of the research on environmental (micro)plastics to stimulate research and call for papers.
Background: Different flavonoids are known to interfere with influenza A virus replication. Recently, we showed that the structurally similar flavonoids baicalein and biochanin A inhibit highly pathogenic avian H5N1 influenza A virus replication by different mechanisms in A549 lung cells. Here, we investigated the effects of both compounds on H5N1-induced reactive oxygen species (ROS) formation and the role of ROS formation during H5N1 replication.
Findings: Baicalein and biochanin A enhanced H5N1-induced ROS formation in A549 cells and primary human monocyte-derived macrophages. Suppression of ROS formation induced by baicalein and biochanin A using the antioxidant N-acetyl-L-cysteine strongly increased the anti-H5N1 activity of both compounds in A549 cells but not in macrophages.
Conclusions: These findings emphasise that flavonoids induce complex pharmacological actions some of which may interfere with H5N1 replication while others may support H5N1 replication. A more detailed understanding of these actions and the underlying structure-activity relationships is needed to design agents with optimised anti-H5N1 activity.
Background: Dysregulation of the autonomic nervous system is frequent in subjects with cardiovascular disease. The contribution of different forms of renovascular hypertension and the mechanisms contributing to autonomic dysfunction in hypertension are incompletely understood. Here, murine models of renovascular hypertension with preserved (2-kidneys-1 clip, 2K1C) and reduced (1-kidney-1 clip, 1K1C) kidney mass were studied with regard to autonomic nervous system regulation (sympathetic tone: power-spectral analysis of systolic blood pressure; parasympathetic tone: power-spectral analysis of heart rate) and baroreflex sensitivity of heart rate by spontaneous, concomitant changes of systolic blood pressure and pulse interval. Involvement of the renin-angiotensin system and the rho-kinase pathway were determined by application of inhibitors.
Results: C57BL6N mice (6 to 11) with reduced kidney mass (1K1C) or with preserved kidney mass (2K1C) developed a similar degree of hypertension. In comparison to control mice, both models presented with a significantly increased sympathetic tone and lower baroreflex sensitivity of heart rate. However, only 2K1C animals had a lower parasympathetic tone, whereas urinary norepinephrine excretion was reduced in the 1K1C model. Rho kinase inhibition given to a subset of 1K1C and 2K1C animals improved baroreflex sensitivity of heart rate selectively in the 1K1C model. Rho kinase inhibition had no additional effects on autonomic nervous system in either model of renovascular hypertension and did not change the blood pressure. Blockade of AT1 receptors (in 2K1C animals) normalized the sympathetic tone, decreased resting heart rate, improved baroreflex sensitivity of heart rate and parasympathetic tone.
Conclusions: Regardless of residual renal mass, blood pressure and sympathetic tone are increased, whereas baroreflex sensitivity is depressed in murine models of renovascular hypertension. Reduced norepinephrine excretion and/or degradation might contribute to sympathoactivation in renovascular hypertension with reduced renal mass (1K1C). Overall, the study helps to direct research to optimize medical therapy of hypertension.
Background: High-intensity focused ultrasound (HIFU) allows to inflict intracorporal thermal lesions without penetrating the skin or damaging the surrounding tissue. This analysis intends to assess the magnitude of HIFU-induced ablations within benign thyroid nodules using scintigraphic imaging with 99mTc.
Methods: Ten cold, hot, or indifferent nodules were treated using multiple pulses of HIFU to induce temperatures of around 85°C within the ablation zone. Pre- and posttreatment, uptake values of 99mTc pertechnetate or 99mTc-MIBI were recorded. The pre-post reduction of nodular uptake was evaluated to assess ablation magnitude.
Results: Relative nodular uptake in relation to total thyroidal uptake decreased after one session of HIFU in all cases. Median 99mTc-MIBI uptake reduction was 35.5% (ranging from 11% to 57%; p < 0.1), while 99mTc-pertechnetate scintigraphy showed a median uptake reduction of 27% (range 10% to 44%; p < 0.1). No major complications were observed.
Conclusions: HIFU appears to be safe and is an easy to perform means of thermal ablation. This study shows that HIFU treatment in thyroidal nodules can be evaluated by scintigraphic means shortly after the intervention. Due to small sample size, the exact magnitude of HIFU ablation efficiency in thyroidal nodules remains a value to beassessed in a larger study.
Background: The current taxonomy of the African giraffe (Giraffa camelopardalis) is primarily based on pelage pattern and geographic distribution, and nine subspecies are currently recognized. Although genetic studies have been conducted, their resolution is low, mainly due to limited sampling. Detailed knowledge about the genetic variation and phylogeography of the South African giraffe (G. c. giraffa) and the Angolan giraffe (G. c. angolensis) is lacking. We investigate genetic variation among giraffe matrilines by increased sampling, with a focus on giraffe key areas in southern Africa.
Results: The 1,562 nucleotides long mitochondrial DNA dataset (cytochrome b and partial control region) comprises 138 parsimony informative sites among 161 giraffe individuals from eight populations. We additionally included two okapis as an outgroup. The analyses of the maternally inherited sequences reveal a deep divergence between northern and southern giraffe populations in Africa, and a general pattern of distinct matrilineal clades corresponding to their geographic distribution. Divergence time estimates among giraffe populations place the deepest splits at several hundred thousand years ago.
Conclusions: Our increased sampling in southern Africa suggests that the distribution ranges of the Angolan and South African giraffe need to be redefined. Knowledge about the phylogeography and genetic variation of these two maternal lineages is crucial for the development of appropriate management strategies.
Hereditary angioedema (HAE) is a disease which is associated with random and often unpredictable attacks of painful swelling typically affecting the extremities, bowel mucosa, genitals, face and upper airway. Attacks are associated with significant functional impairment, decreased Health Related Quality of Life, and mortality in the case of laryngeal attacks. Caring for patients with HAE can be challenging due to the complexity of this disease. The care of patients with HAE in Canada is neither optimal nor uniform across the country. It lags behind other countries where there are more organized models for HAE management, and where additional therapeutic options are licensed and available for use. The objective of this guideline is to provide graded recommendations for the management of patients in Canada with HAE. This includes the treatment of attacks, short-term prophylaxis, long-term prophylaxis, and recommendations for self-administration, individualized therapy, quality of life, and comprehensive care. It is anticipated that by providing this guideline to caregivers, policy makers, patients and their advocates, that there will be an improved understanding of the current recommendations regarding management of HAE and the factors that need to be considered when choosing therapies and treatment plans for individual patients. The primary target users of this guideline are healthcare providers who are managing patients with HAE. Other healthcare providers who may use this guideline are emergency physicians, gastroenterologists, dentists and otolaryngologists, who will encounter patients with HAE and need to be aware of this condition. Hospital administrators, insurers and policy makers may also find this guideline helpful.
Background: Malaria is still a priority public health problem of Nepal where about 84% of the population are at risk. The aim of this paper is to highlight the past and present malaria situation in this country and its challenges for long-term malaria elimination strategies.
Methods: Malariometric indicator data of Nepal recorded through routine surveillance of health facilities for the years between 1963 and 2012 were compiled. Trends and differences in malaria indicator data were analysed.
Results: The trend of confirmed malaria cases in Nepal between 1963 and 2012 shows fluctuation, with a peak in 1985 when the number exceeded 42,321, representing the highest malaria case-load ever recorded in Nepal. This was followed by a steep declining trend of malaria with some major outbreaks. Nepal has made significant progress in controlling malaria transmission over the past decade: total confirmed malaria cases declined by 84% (12,750 in 2002 vs 2,092 in 2012), and there was only one reported death in 2012. Based on the evaluation of the National Malaria Control Programme in 2010, Nepal recently adopted a long-term malaria elimination strategy for the years 2011–2026 with the ambitious vision of a malaria-free Nepal by 2026. However, there has been an increasing trend of Plasmodium falciparum and imported malaria proportions in the last decade. Furthermore, the analysis of malariometric indicators of 31 malaria-risk districts between 2004 and 2012 shows a statistically significant reduction in the incidence of confirmed malaria and of Plasmodium vivax, but not in the incidence of P. falciparum and clinically suspected malaria.
Conclusions: Based on the achievements the country has made over the last decade, Nepal is preparing to move towards malaria elimination by 2026. However, considerable challenges lie ahead. These include especially, the need to improve access to diagnostic facilities to confirm clinically suspected cases and their treatment, the development of resistance in parasites and vectors, climate change, and increasing numbers of imported cases from a porous border with India. Therefore, caution is needed before the country embarks towards malaria elimination.
Background: Advanced non-small cell lung cancer (NSCLC) represents a significant unmet medical need. Despite advances with targeted therapies in a small subset of patients, fewer than 20% of patients survive for more than two years after diagnosis. Cancer vaccines are a promising therapeutic approach that offers the potential for durable responses through the engagement of the patient's own immune system. CV9202 is a self-adjuvanting mRNA vaccine that targets six antigens commonly expressed in NSCLC (NY ESO-1, MAGEC1, MAGEC2, 5 T4, survivin, and MUC1).
Methods/Design: The trial will assess the safety and tolerability of CV9202 vaccination combined with local radiation designed to enhance immune responses and will include patients with stage IV NSCLC and a response or stable disease after first-line chemotherapy or therapy with an EGFR tyrosine kinase inhibitor. Three histological and molecular subtypes of NSCLC will be investigated (squamous and non-squamous cell with/without EGFR mutations). All patients will receive two initial vaccinations with CV9202 prior to local radiotherapy (5 GY per day for four successive days) followed by further vaccinations until disease progression. The primary endpoint of the study is the number of patients experiencing Grade >3 treatment-related adverse events. Pharmacodynamic analyses include the assessment of immune responses to the antigens encoded by CV9202 and others not included in the panel (antigen spreading) and standard efficacy assessments.
Discussion: RNActive self-adjuvanted mRNA vaccines offer the potential for simultaneously inducing immune responses to a wide panel of antigens commonly expressed in tumors. This trial will assess the feasibility of this approach in combination with local radiotherapy in NSCLC patients.
Altered mucosal immune response after acute lung injury in a murine model of Ataxia Telangiectasia
(2014)
Background: Ataxia telangiectasia (A-T) is a rare but devastating and progressive disorder characterized by cerebellar dysfunction, lymphoreticular malignancies and recurrent sinopulmonary infections. In A-T, disease of the respiratory system causes significant morbidity and is a frequent cause of death.
Methods: We used a self-limited murine model of hydrochloric acid-induced acute lung injury (ALI) to determine the inflammatory answer due to mucosal injury in Atm (A-T mutated)- deficient mice (Atm−/−).
Results: ATM deficiency increased peak lung inflammation as demonstrated by bronchoalveolar lavage fluid (BALF) neutrophils and lymphocytes and increased levels of BALF pro-inflammatory cytokines (e.g. IL-6, TNF). Furthermore, bronchial epithelial damage after ALI was increased in Atm−/− mice. ATM deficiency increased airway resistance and tissue compliance before ALI was performed.
Conclusions: Together, these findings indicate that ATM plays a key role in inflammatory response after airway mucosal injury.
Antigenic and 3D structural characterization of soluble X4 and hybrid X4-R5 HIV-1 Env trimers
(2014)
Background: HIV-1 is decorated with trimeric glycoprotein spikes that enable infection by engaging CD4 and a chemokine coreceptor, either CCR5 or CXCR4. The variable loop 3 (V3) of the HIV-1 envelope protein (Env) is the main determinant for coreceptor usage. The predominant CCR5 using (R5) HIV-1 Env has been intensively studied in function and structure, whereas the trimeric architecture of the less frequent, but more cytopathic CXCR4 using (X4) HIV-1 Env is largely unknown, as are the consequences of sequence changes in and near V3 on antigenicity and trimeric Env structure.
Results: Soluble trimeric gp140 Env constructs were used as immunogenic mimics of the native spikes to analyze their antigenic properties in the context of their overall 3D structure. We generated soluble, uncleaved, gp140 trimers from a prototypic T-cell line-adapted (TCLA) X4 HIV-1 strain (NL4-3) and a hybrid (NL4-3/ADA), in which the V3 spanning region was substituted with that from the primary R5 isolate ADA. Compared to an ADA (R5) gp140, the NL4-3 (X4) construct revealed an overall higher antibody accessibility, which was most pronounced for the CD4 binding site (CD4bs), but also observed for mAbs against CD4 induced (CD4i) epitopes and gp41 mAbs. V3 mAbs showed significant binding differences to the three constructs, which were refined by SPR analysis. Of interest, the NL4-3/ADA construct with the hybrid NL4-3/ADA CD4bs showed impaired CD4 and CD4bs mAb reactivity despite the presence of the essential elements of the CD4bs epitope. We obtained 3D reconstructions of the NL4-3 and the NL4-3/ADA gp140 trimers via electron microscopy and single particle analysis, which indicates that both constructs inherit a propeller-like architecture. The first 3D reconstruction of an Env construct from an X4 TCLA HIV-1 strain reveals an open conformation, in contrast to recently published more closed structures from R5 Env. Exchanging the X4 V3 spanning region for that of R5 ADA did not alter the open Env architecture as deduced from its very similar 3D reconstruction.
Conclusions: 3D EM analysis showed an apparent open trimer configuration of X4 NL4-3 gp140 that is not modified by exchanging the V3 spanning region for R5 ADA.
Tubulin-binding agents such as taxol, vincristine or vinblastine are well-established drugs in clinical treatment of metastatic cancer. However, because of their highly complex chemical structures, the synthesis and hence the supply issues are still quite challenging. Here we set on stage pretubulysin, a chemically accessible precursor of tubulysin that was identified as a potent microtubule-binding agent produced by myxobacteria. Although much simpler in chemical structure, pretubulysin abrogates proliferation and long-term survival as well as anchorage-independent growth, and also induces anoikis and apoptosis in invasive tumor cells equally potent to tubulysin. Moreover, pretubulysin posseses in vivo efficacy shown in a chicken chorioallantoic membrane (CAM) model with T24 bladder tumor cells, in a mouse xenograft model using MDA-MB-231 mammary cancer cells and finally in a model of lung metastasis induced by 4T1 mouse breast cancer cells. Pretubulysin induces cell death via the intrinsic apoptosis pathway by abrogating the expression of pivotal antiapoptotic proteins, namely Mcl-1 and Bcl-xL, and shows distinct chemosensitizing properties in combination with TRAIL in two- and three-dimensional cell culture models. Unraveling the underlying signaling pathways provides novel information: pretubulysin induces proteasomal degradation of Mcl-1 by activation of mitogen-activated protein kinase (especially JNK (c-Jun N-terminal kinase)) and phosphorylation of Mcl-1, which is then targeted by the SCF(Fbw7) E3 ubiquitin ligase complex for ubiquitination and degradation. In sum, we designate the microtubule-destabilizing compound pretubulysin as a highly promising novel agent for mono treatment and combinatory treatment of invasive cancer.
DNA methylation reader MECP2 : cell type- and differentiation stage-specific protein distribution
(2014)
Background: Methyl-CpG binding protein 2 (MECP2) is a protein that specifically binds methylated DNA, thus regulating transcription and chromatin organization. Mutations in the gene have been identified as the principal cause of Rett syndrome, a severe neurological disorder. Although the role of MECP2 has been extensively studied in nervous tissues, still very little is known about its function and cell type specific distribution in other tissues.
Results: Using immunostaining on tissue cryosections, we characterized the distribution of MECP2 in 60 cell types of 16 mouse neuronal and non-neuronal tissues. We show that MECP2 is expressed at a very high level in all retinal neurons except rod photoreceptors. The onset of its expression during retina development coincides with massive synapse formation. In contrast to astroglia, retinal microglial cells lack MECP2, similar to microglia in the brain, cerebellum, and spinal cord. MECP2 is also present in almost all non-neural cell types, with the exception of intestinal epithelial cells, erythropoietic cells, and hair matrix keratinocytes. Our study demonstrates the role of MECP2 as a marker of the differentiated state in all studied cells other than oocytes and spermatogenic cells. MECP2-deficient male (Mecp2−/y) mice show no apparent defects in the morphology and development of the retina. The nuclear architecture of retinal neurons is also unaffected as the degree of chromocenter fusion and the distribution of major histone modifications do not differ between Mecp2−/y and Mecp2wt mice. Surprisingly, the absence of MECP2 is not compensated by other methyl-CpG binding proteins. On the contrary, their mRNA levels were downregulated in Mecp2−/y mice.
Conclusions: MECP2 is almost universally expressed in all studied cell types with few exceptions, including microglia. MECP2 deficiency does not change the nuclear architecture and epigenetic landscape of retinal cells despite the missing compensatory expression of other methyl-CpG binding proteins. Furthermore, retinal development and morphology are also preserved in Mecp2-null mice. Our study reveals the significance of MECP2 function in cell differentiation and sets the basis for future investigations in this direction.
Immunotherapy of cancer utilizes dendritic cells (DCs) for antigen presentation and the induction of tumor-specific immune responses. However, the therapeutic induction of anti-tumor immunity is limited by tumor escape mechanisms. In this study, immortalized dendritic D2SC/1 cells were transduced with a mutated version of the p53 tumor suppressor gene, p53M234I, or p53C132F/E168G, which are overexpressed in MethA fibrosarcoma tumor cells. In addition, D2SC/1 cells were fused with MethA tumor cells to generate a vaccine that potentially expresses a large repertoire of tumor-antigens. Cellular vaccines were transplanted onto Balb/c mice and MethA tumor growth and anti-tumor immune responses were examined in vaccinated animals. D2SC/1-p53M234I and D2SC/1-p53C132F/E168G cells induced strong therapeutic and protective MethA tumor immunity upon transplantation in Balb/c mice. However, in a fraction of immunized mice MethA tumor growth resumed after an extended latency period. Analysis of these tumors indicated loss of p53 expression. Mice, pre-treated with fusion hybrids generated from D2SC/1 and MethA tumor cells, suppressed MethA tumor growth and averted adaptive immune escape. Polyclonal B-cell responses directed against various MethA tumor proteins could be detected in the sera of D2SC/1-MethA inoculated mice. Athymic nude mice and Balb/c mice depleted of CD4(+) or CD8(+) T-cells were not protected against MethA tumor cell growth after immunization with D2SC/1-MethA hybrids. Our results highlight a potential drawback of cancer immunotherapy by demonstrating that the induction of a specific anti-tumor response favors the acquisition of tumor phenotypes promoting immune evasion. In contrast, the application of DC/tumor cell fusion hybrids prevents adaptive immune escape by a T-cell dependent mechanism and provides a simple strategy for personalized anti-cancer treatment without the need of selectively priming the host immune system.
FLRTs are broadly expressed proteins with the unique property of acting as homophilic cell adhesion molecules and as heterophilic repulsive ligands of Unc5/Netrin receptors. How these functions direct cell behavior and the molecular mechanisms involved remain largely unclear. Here we use X-ray crystallography to reveal the distinct structural bases for FLRT-mediated cell adhesion and repulsion in neurons. We apply this knowledge to elucidate FLRT functions during cortical development. We show that FLRTs regulate both the radial migration of pyramidal neurons, as well as their tangential spread. Mechanistically, radial migration is controlled by repulsive FLRT2-Unc5D interactions, while spatial organization in the tangential axis involves adhesive FLRT-FLRT interactions. Further, we show that the fundamental mechanisms of FLRT adhesion and repulsion are conserved between neurons and vascular endothelial cells. Our results reveal FLRTs as powerful guidance factors with structurally encoded repulsive and adhesive surfaces.
Cryo-electron tomography provides a snapshot of the cellular proteome. With template matching, the spatial positions of various macromolecular complexes within their native cellular context can be detected. However, the growing awareness of the reference bias introduced by the cross-correlation based approaches, and more importantly the lack of a reliable confidence measurement in the selection of these macromolecular complexes, has restricted the use of these applications. Here we propose a heuristic, in which the reference bias is measured in real space in an analogous way to the R-free value in X-ray crystallography. We measure the reference bias within the mask used to outline the area of the template, and do not modify the template itself. The heuristic works by splitting the mask into a working and a testing area in a volume ratio of 9:1. While the working area is used during the calculation of the cross-correlation function, the information from both areas is explored to calculate the M-free score. We show using artificial data, that the M-free score gives a reliable measure for the reference bias. The heuristic can be applied in template matching and in sub-tomogram averaging. We further test the applicability of the heuristic in tomograms of purified macromolecules, and tomograms of whole Mycoplasma cells.
Correlative microscopy incorporates the specificity of fluorescent protein labeling into high-resolution electron micrographs. Several approaches exist for correlative microscopy, most of which have used the green fluorescent protein (GFP) as the label for light microscopy. Here we use chemical tagging and synthetic fluorophores instead, in order to achieve protein-specific labeling, and to perform multicolor imaging. We show that synthetic fluorophores preserve their post-embedding fluorescence in the presence of uranyl acetate. Post-embedding fluorescence is of such quality that the specimen can be prepared with identical protocols for scanning electron microscopy (SEM) and transmission electron microscopy (TEM); this is particularly valuable when singular or otherwise difficult samples are examined. We show that synthetic fluorophores give bright, well-resolved signals in super-resolution light microscopy, enabling us to superimpose light microscopic images with a precision of up to 25 nm in the x-y plane on electron micrographs. To exemplify the preservation quality of our new method we visualize the molecular arrangement of cadherins in adherens junctions of mouse epithelial cells.
Bacteria have adapted their NhaA Na(+)/H(+) exchangers responsible for salt homeostasis to their different habitats. We present an electrophysiological and kinetic analysis of NhaA from Helicobacter pylori and compare it to the previously investigated exchangers from Escherichia coli and Salmonella typhimurium. Properties of all three transporters are described by a simple model using a single binding site for H(+) and Na(+). We show that H.pylori NhaA only has a small acidic shift of its pH-dependent activity profile compared to the other transporters and discuss why a more drastic change in its pH activity profile is not physiologically required.
Survivin is a well-established target in experimental cancer therapy. The molecule is over-expressed in most human tumors, but hardly detectable in normal tissues. Multiple functions in different subcellular compartments have been assigned. It participates in the control of cell division, apoptosis, the cellular stress response, and also in the regulation of cell migration and metastasis. Survivin expression has been recognized as a biomarker: high expression indicates an unfavorable prognosis and resistance to chemotherapeutic agents and radiation treatment. Survivin is an unconventional drug target and several indirect approaches have been exploited to affect its function and the phenotype of survivin-expressing cells. Interference with the expression of the survivin gene, the utilization of its messenger RNA, the intracellular localization, the interaction with binding partners, the stability of the survivin protein, and the induction of survivin-specific immune responses have been taken into consideration. A direct strategy to inhibit survivin has been based on the identification of a specifically interacting peptide. This peptide can recognize survivin intracellularly and cause the degradation of the ligand–survivin complex. Technology is being developed that might allow the derivation of small molecular-weight, drug-like compounds that are functionally equivalent to the peptide ligand.
Die Naturwissenschaften waren von den teilweise gewalttätigen Auseinandersetzungen der Studentenproteste Ende der 1960er Jahre nicht an erster Stelle betroffen. Insbesondere das Pharmaziestudium mit seinem zeitintensiven, streng geregelten und durch Laborpraktika dominierten Arbeitsalltag bot wenig Raum für politische Agitationen. Andererseits waren die Studierenden auch nicht mit den Herausforderungen einer sich entwickelnden Massenuniversität konfrontiert. Nichtsdestoweniger mussten sich auch die Hochschullehrer der naturwissenschaftlichen Fakultät mit den zeitgenössischen Reformvorschlägen auseinandersetzen. Der pharmazeutische Chemiker Herbert Oelschläger, eine der prägenden Persönlichkeiten der Frankfurter Pharmazie, scheute diese Auseinandersetzungen nicht und wurde deshalb zu einer beliebten Zielscheibe des AStA.
Der "diskus" war in den 1970er Jahren mehr als eine Studentenzeitung. Die Blattmacher boten der linken Sponti-Szene in Frankfurt, aber auch Schriftstellern wie Erich Fried dort ein publizistisches Forum. Das Themenspektrum reichte von dem Häuserkampf im Westend bis zur Situation der linken Intellektuellen in der Bundesrepublik, nachdem sich das innenpolitische Klima infolge der RAF-Anschläge verschärft hatte.
War "68" nur der mythologische Name für Ereignisse und Entwicklungen, die schon viel früher begannen und sich deutlich länger hinzogen? Fühlte sich die immobil gewordene Gesellschaft in der Phase nach dem Wiederaufbau durch die Studentenrevolte von sich selbst befreit? Was hat die "Bewegungsgesellschaft" ab den 1970er Jahren mit "68" zu tun? Diesen Fragen geht der Soziologe Heinz Bude in seinem Essay nach.
Philologe im "Kriegseinsatz" : der Frankfurter Germanist Julius Petersen und der Erste Weltkrieg
(2014)
Vorlesungen für Studenten und Bildungsangebote für Bürger – wie lässt sich dieser Anspruch der jungen Stiftungsuniversität auch in Zeiten des Krieges realisieren, wenn Professoren wie Studenten ins Feld ziehen müssen? Das Beispiel des Germanisten Julius Petersen zeigt, welche Anstrengungen zwischen 1914 und 1918 unternommen wurden, um "Volksbildung" und "Vaterländischen Unterricht" zu ermöglichen. Dazu gehörten Vorträge an der Front ebenso wie Bürgervorlesungen in der Heimat.
Chronic ethanol abuse is known to increase susceptibility to infections after injury, in part, by modification of macrophage function. Several intracellular signalling mechanisms are involved in the initiation of inflammatory responses, including the nuclear factor-κB (NF-κB) pathway. In this study, we investigated the systemic and hepatic effect of chronic ethanol feeding on in vivo activation of NF-κB in NF-κB(EGFP) reporter gene mice. Specifically, the study focused on Kupffer cell proinflammatory cytokines IL-6 and TNF-α and activation of NF-κB after chronic ethanol feeding followed by in vitro stimulation with lipopolysaccharide (LPS). We found that chronic ethanol upregulated NF-κB activation and increased hepatic and systemic proinflammatory cytokine levels. Similarly, LPS-stimulated IL-1 β release from whole blood was significantly enhanced in ethanol-fed mice. However, LPS significantly increased IL-6 and TNF-α levels. These results demonstrate that chronic ethanol feeding can improve the responsiveness of macrophage LPS-stimulated IL-6 and TNF-α production and indicate that this effect may result from ethanol-induced alterations in intracellular signalling through NF-κB. Furthermore, LPS and TNF-α stimulated the gene expression of different inflammatory mediators, in part, in a NF-κB-dependent manner.
Der folgende kleine Aufsatz lobt einen Wissenschaftler, der noch lebt: Prof. Dr. Heiko Braak. Und seine Frau, Prof. Dr. Eva Braak, die leider schon gestorben ist. Die beiden Braaks waren Hirnforscher an der Dr. Senckenbergischen Anatomie der Goethe-Universität. Da hat der Autor des Aufsatzes, Helmut Wicht, sie kennengelernt, als er selbst noch ein junger Anatom war. Und hat die Braaks, ihre Forschung, aber auch die ästhetische Attitüde, mit der vor allem Herr Braak die Sache anging, ebenso wie die Schönheit des Gehirns zu schätzen gelernt. Davon, von der Schönheit, handelt der Aufsatz.
Die Erkenntnis, dass das Gehirn Hormone produziert, gehört heute zum Allgemeingut des biomedizinischen Wissens. Ausgangspunkt der modernen Neuroendokrinologie ist das weit gespannte biologische Konzept der Neurosekretion, das Ernst und Berta Scharrer in den 1930er Jahren aus einer Reihe von fundamentalen Einzelentdeckungen entwickelten. Das Fundament dieses Konzeptes legte das Paar am Neurologischen Institut (Edinger Institut) in Frankfurt am Main.
Zu den exzellenten Frankfurter Neurowissenschaftlern des 20. Jahrhunderts zählt Kurt Goldstein. Er durchlief die harte Schule von Ludwig Edinger. Bekannt wurde er jedoch durch einen eigenständigen Ansatz, der mit dem Schlagwort ganzheitliche Neurologie charakterisiert werden kann. Er wandte sich gegen die Auffassung, »Funktionen« im Gehirn exakt lokalisieren zu können, ohne den lokalisatorischen Ansatz vollständig zu verwerfen. Besondere Aufmerksamkeit schenkte er den Kompensationsreaktionen des Gehirns und des »ganzen« Menschen. » […] he never forgot that he addressed an individual, not a brain«, brachte es sein Schüler Walther Riese auf den Punkt.
Unter den zahlreichen Traditionen, an die in Frankfurt am Main stolz erinnert wird, bleibt eine bislang eigentümlich unterbelichtet: die Geschichte der Hirnforschung. Gerald Kreft gibt einen Überblick über dieses faszinierende Kapitel der lokalen Wissenschaftsentwicklung und stellt zugleich das Museumsprojekt zur Geschichte der Hirnforschung in Frankfurt vor, das die Ludwig Edinger-Stiftung realisieren will. Hier wirkt jener Geist fort, der 1914 zur Eröffnung der Goethe-Universität führte. Der Hirnforscher Ludwig Edinger (1855-1918) war der einzige Wissenschaftler unter den elf Unterzeichnern des Stiftungsvertrags, der an der Universität forschte und lehrte.
Was für den Laien unscheinbar aussieht, kann für den Geologen ein wertvolles Fundstück sein. Um ihren Blick zu schulen, arbeiten Studierende nicht nur im Gelände, sondern auch mit den Objekten der geowissenschaftlichen Sammlungen. Für die Forschung sind die Fundstücke ein steinernes Gedächtnis der Erdgeschichte.
Das Sofa Arthur Schopenhauers, Millionen Jahre alte Fossilien, japanische Mangas, physikalische Geräte, illustrierte Inkunabeln, hauchdünne Hirnschnitte, Kopien afrikanischer Felsbilder, Herbarbelege von James Cook, Klavierrollen mit Einspielungen von Camille Saint Saens ... Was sich liest wie das schillernde Inventar eines Universalmuseums zur Erd- und Menschheitsgeschichte der vergangenen 4,6 Milliarden Jahre ist das dingliche Reservoir der historischen und aktuellen Forschung und Lehre an der Goethe-Universität. Eine Ausstellung im Museum Giersch zeigt anlässlich der 100-Jahr-Feier ausgewählte Schätze aus 40 Sammlungen für ein breites Publikum.
Neue Forschungsmethoden verändern oft auch die Bedeutung von Fachsammlungen. Häufig verläuft dieser Wandel zu einer Sammlung von nunmehr historischem Wert schleichend. Manchmal werden Sammlungen auch durch neue Fragestellungen für andere Fachwissenschaften unerwartet wertvoll. Gastautor Jochen Hennig, Sammlungsbeauftragter des Präsidiums der Humboldt-Universität zu Berlin, plädiert dafür, den Bedeutungswandel von Universitätssammlungen aktiv zu begleiten.
Wissenschaft findet nicht nur im Labor statt. Sie ist eingebettet in ein soziales und wirtschaftliches Gefüge. Dieses kommt besonders dann zum Ausdruck, wenn Kontroversen über die Interpretation von Experimenten entstehen. Ein Beispiel dafür ist Prof. Dr. Rolf Marschaleks Theorie zur Entstehung bestimmter Leukämien. Der Frankfurter Forscher hält die über viele Jahre als richtig akzeptierte Theorie seiner bekannten amerikanischen Kollegin Janet Rowley für zu eng gefasst – und macht sich damit in der Fachwelt jenseits des Atlantiks nicht nur Freunde.
Inter- und Transdisziplinarität sind ein Versuch, das Spezialwissen verschiedener Disziplinen miteinander zu verbinden, um die komplexen Fragestellungen unserer Zeit beantworten zu können. Beate Meichsner hat im Gespräch mit Wissenschaftlern unterschiedlichster Disziplinen Chancen und Grenzen, Möglichkeiten und Stolpersteine interdisziplinärer und transdisziplinärer Forschung eruiert.
Die Mathematik ist die einzige Wissenschaft, in der Wissen nicht veraltet. Das hängt damit zusammen, dass sie ein geistiges Konstrukt ist, das zuallererst im Kopf der Mathematiker entsteht. Zwar gibt es heute manche Teilgebiete wie die angewandte Mathematik, die praxisbezogene Probleme unter Aufwendung großer Rechnerleistungen lösen, doch Gebiete wie die reine Mathematik benötigen den PC nur zum Testen von Hypothesen. Dennoch hat sich die Arbeitsweise der Mathematiker in den letzten Jahrzehnten verändert.
Manche Wissenschaftler haben die Gabe, andere zu inspirieren. Sie ziehen talentierte junge Menschen an, sind gut vernetzt und bringen wiederum erfolgreiche Forscher hervor. Heike Jüngst spürt dem Erfolgsrezept der Begründer wissenschaftlicher Schulen an einem historischen und einem zeitgenössischen Beispiel nach.
Als Rainer Forst, Professor für politische Theorie und Philosophie an der Frankfurter Universität, 2012 den Leibniz-Preis erhielt, hieß es in der Laudatio, er führe die »philosophische Tradition der Frankfurter Schule mit Jürgen Habermas und Axel Honneth auf höchstem Niveau« fort. In diesem Jahr wird das Frankfurter Institut für Sozialforschung 90 Jahre alt, und die Anfänge der »Frankfurter Schule« liegen ungefähr 85 Jahre zurück – Anlässe genug, um zu fragen: Wie hat sich die »Frankfurter Schule« gewandelt?
Ein neophytisches Schaumkraut, das sich am Bodenseeufer massiv ausgebreitet hat und in jüngster Zeit vielfach auch in Belgien und den Niederlanden beobachtet wurde, konnte als Unkraut in einem Gartencenter, einem Baumarkt und auf drei Friedhöfen in Aachen nachgewiesen werden. Die Art wird als Japanisches Reisfeld-Schaumkraut, Cardamine flexuosa auct., Asian C. flexuosa, C. flexuosa subsp. debilis und aktuell als C. hamiltonii bezeichnet. Offenbar handelt es sich um Erstnachweise für Nordrhein-Westfalen.
Es ist 18:50 Uhr an einem Mittwochabend. Das PA-Gebäude auf dem Campus Westend ist hell erleuchtet. Während draußen die ersten Gäste stehen, ist im Innern ein junger Mann in Hemd und Sakko damit beschäftigt, einen roten Teppich von den letzten Flusen zu befreien. In wenigen Minuten werden die ersten Besucher der Ausstellung »36 Stifter für eine Idee« in den Saal treten, über den frisch gesaugten Teppich laufen und das Ergebnis von drei Jahren Arbeit begutachten.
Erinnerungsorte
(2014)
Immatrikulationsfeiern gehörten zum festen Ritual der universitären Kultur, bis in den 1960er Jahren bewusst mit dieser Tradition gebrochen wurde. Heute werden die Studierenden an der Goethe-Universität beim "unistart" begrüßt. Ist diese Veranstaltung ein Brückenschlag zwischen Gegenwart und alten Zeiten oder eher ein Spiegel des sich wandelnden universitären Selbstverständnisses?
Kollektives und kulturelles Erinnern : Erinnerungskulturen leben von der Dynamik der Gegenwart
(2014)
Keine Gemeinschaft kommt ohne kollektive Erinnerungen aus, dazu gehören Gedenkfeiern und Denkmäler ebenso wie Mythen und Rituale oder die Identifikation mit großen Ereignissen oder Persönlichkeiten. Erinnern ist nicht nur identitätsstiftend, es bedeutet auch, sich vergangene Erlebnisse zu vergegenwärtigen – oder wie Marcel Proust es ausdrückt: "Erst im Gedächtnis formt sich die Wirklichkeit." Wenn die Erinnerungskultur ihre Dynamik aus der Aktualität verliert, ist sie tot.
»Königliche Universität zu Frankfurt a. M.« – mit diesem Namen konnten sich auch die Frankfurter Stifter arrangieren, formalrechtlich hätte Wilhelm II. den Vortritt gehabt. Goethe, natürlich immer fester Bestandteil des philologischen
Bildungskanons, rückte der Universität verhalten näher: zunächst mit seinem Relief über dem historischen Haupteingang, bis es zu seinem 100. Todestag 1932 an der Zeit schien, die Universität nach dem Dichterfürsten zu benennen.
Das Verhältnis zwischen den Frankfurtern und ihrer Universität ist ein wechselvolles: gestiftet und großzügig unterstützt von Bürgern und Stadtpolitikern, gepflegt in den harten Jahren der Inflation, gleichgeschaltet und wissenschaftlich ausgehungert während des Nationalsozialismus, entfremdet und abgelehnt nach der Studentenrevolte in den 1960er und 1970er Jahren, wiederentdeckt ab den 1980er Jahren, geschätzt und gefördert seit der (Rück-)Verwandlung in eine Stiftungsuniversität (2008).
Wie nehmen Sie die Goethe-Universität heute in Zeiten des stärkeren nationalen und internationalen Wettbewerbs der Hochschulen wahr?
Was war rückblickend die wichtigste Veränderung, die Sie während Ihrer Amtszeit initiieren konnten?
Wenn Sie Ihre Zeit als Präsident noch einmal Revue passieren lassen, welche Episode lässt Sie heute noch schmunzeln?
Sie hätten die Chance, 2015 nochmal als Präsident anzutreten, welche Impulse würden Sie dann setzen wollen?
Was wünschen Sie der Goethe-Universität für die nächsten 50 Jahre?
Eine weltoffene, tolerante und liberale Intellektualität prägt die Frankfurter Universität – abgesehen von dem dunklen Kapitel während des Nationalsozialismus – seit ihrer Gründung 1914. Gegründet und gestiftet von wohlhabenden und engagierten Bürgern der Stadt, war sie von Beginn an etwas Besonderes in der deutschen Universitätslandschaft.
Examining event-related potential (ERP) correlates of decision bias in recognition memory judgments
(2014)
Memory judgments can be based on accurate memory information or on decision bias (the tendency to report that an event is part of episodic memory when one is in fact unsure). Event related potentials (ERP) correlates are important research tools for elucidating the dynamics underlying memory judgments but so far have been established only for investigations of accurate old/new discrimination. To identify the ERP correlates of bias, and observe how these interact with ERP correlates of memory, we conducted three experiments that manipulated decision bias within participants via instructions during recognition memory tests while their ERPs were recorded. In Experiment 1, the bias manipulation was performed between blocks of trials (automatized bias) and compared to trial-by-trial shifts of bias in accord with an external cue (flexibly controlled bias). In Experiment 2, the bias manipulation was performed at two different levels of accurate old/new discrimination as the memory strength of old (studied) items was varied. In Experiment 3, the bias manipulation was added to another, bottom-up driven manipulation of bias induced via familiarity. In the first two Experiments, and in the low familiarity condition of Experiment 3, we found evidence of an early frontocentral ERP component at 320 ms poststimulus (the FN320) that was sensitive to the manipulation of bias via instruction, with more negative amplitudes indexing more liberal bias. By contrast, later during the trial (500–700 ms poststimulus), bias effects interacted with old/new effects across all three experiments. Results suggest that the decision criterion is typically activated early during recognition memory trials, and is integrated with retrieved memory signals and task-specific processing demands later during the trial. More generally, the findings demonstrate how ERPs can help to specify the dynamics of recognition memory processes under top-down and bottom-up controlled retrieval conditions.