Refine
Year of publication
Document Type
- Article (31440) (remove)
Language
- English (16045)
- German (13387)
- Portuguese (696)
- French (387)
- Croatian (251)
- Spanish (250)
- Italian (134)
- Turkish (113)
- Multiple languages (36)
- Latin (35)
Has Fulltext
- yes (31440)
Keywords
- Deutsch (503)
- taxonomy (451)
- Literatur (299)
- new species (194)
- Hofmannsthal, Hugo von (185)
- Rezeption (178)
- Übersetzung (163)
- Filmmusik (155)
- Johann Wolfgang von Goethe (131)
- Vormärz (117)
Institute
- Medizin (5409)
- Physik (1959)
- Biowissenschaften (1152)
- Biochemie und Chemie (1113)
- Extern (1108)
- Gesellschaftswissenschaften (803)
- Frankfurt Institute for Advanced Studies (FIAS) (753)
- Geowissenschaften (593)
- Präsidium (453)
- Philosophie (448)
Spontaneous brain activity is characterized in part by a balanced asynchronous chaotic state. Cortical recordings show that excitatory (E) and inhibitory (I) drivings in the E-I balanced state are substantially larger than the overall input. We show that such a state arises naturally in fully adapting networks which are deterministic, autonomously active and not subject to stochastic external or internal drivings. Temporary imbalances between excitatory and inhibitory inputs lead to large but short-lived activity bursts that stabilize irregular dynamics. We simulate autonomous networks of rate-encoding neurons for which all synaptic weights are plastic and subject to a Hebbian plasticity rule, the flux rule, that can be derived from the stationarity principle of statistical learning. Moreover, the average firing rate is regulated individually via a standard homeostatic adaption of the bias of each neuron’s input-output non-linear function. Additionally, networks with and without short-term plasticity are considered. E-I balance may arise only when the mean excitatory and inhibitory weights are themselves balanced, modulo the overall activity level. We show that synaptic weight balance, which has been considered hitherto as given, naturally arises in autonomous neural networks when the here considered self-limiting Hebbian synaptic plasticity rule is continuously active.
Oxidized phospholipids (oxPAPC) induce endothelial dysfunction and atherosclerosis. Here we show that oxPAPC induce a gene network regulating serine-glycine metabolism with the mitochondrial methylenetetrahydrofolate dehydrogenase/cyclohydrolase (MTHFD2) as a causal regulator using integrative network modeling and Bayesian network analysis in human aortic endothelial cells. The cluster is activated in human plaque material and by atherogenic lipoproteins isolated from plasma of patients with coronary artery disease (CAD). Single nucleotide polymorphisms (SNPs) within the MTHFD2-controlled cluster associate with CAD. The MTHFD2-controlled cluster redirects metabolism to glycine synthesis to replenish purine nucleotides. Since endothelial cells secrete purines in response to oxPAPC, the MTHFD2-controlled response maintains endothelial ATP. Accordingly, MTHFD2-dependent glycine synthesis is a prerequisite for angiogenesis. Thus, we propose that endothelial cells undergo MTHFD2-mediated reprogramming toward serine-glycine and mitochondrial one-carbon metabolism to compensate for the loss of ATP in response to oxPAPC during atherosclerosis.
Objective: We present the statistical analysis plan of a prespecified Tranexamic Acid for Hyperacute Primary Intracerebral Haemorrhage (TICH)-2 sub-study aiming to investigate, if tranexamic acid has a different effect in intracerebral haemorrhage patients with the spot sign on admission compared to spot sign negative patients. The TICH-2 trial recruited above 2000 participants with intracerebral haemorrhage arriving in hospital within 8 h after symptom onset. They were included irrespective of radiological signs of on-going haematoma expansion. Participants were randomised to tranexamic acid versus matching placebo. In this subgroup analysis, we will include all participants in TICH-2 with a computed tomography angiography on admission allowing adjudication of the participants’ spot sign status.
Results: Primary outcome will be the ability of tranexamic acid to limit absolute haematoma volume on computed tomography at 24 h (± 12 h) after randomisation among spot sign positive and spot sign negative participants, respectively. Within all outcome measures, the effect of tranexamic acid in spot sign positive/negative participants will be compared using tests of interaction. This sub-study will investigate the important clinical hypothesis that spot sign positive patients might benefit more from administration of tranexamic acid compared to spot sign negative patients.
Trial registration: ISRCTN93732214 (http://www.isrctn.com)
Background: Early-life institutional deprivation produces disinhibited social engagement (DSE). Portrayed as a childhood condition, little is known about the persistence of DSE-type behaviours into, presentation during, and their impact on, functioning in adulthood.
Aims: We examine these issues in the young adult follow-up of the English and Romanian Adoptees study.
Method: A total of 122 of the original 165 Romanian adoptees who had spent up to 43 months as children in Ceauşescu's Romanian orphanages and 42 UK adoptees were assessed for DSE behaviours, neurodevelopmental and mental health problems, and impairment between ages 2 and 25 years.
Results: Young adult DSE behaviour was strongly associated with early childhood deprivation, with a sixfold increase for those who spent more than 6 months in institutions. However, although DSE overlapped with autism spectrum disorder and attention-deficit hyperactivity disorder symptoms it was not, in itself, related to broader patterns of mental health problems or impairments in daily functioning in young adulthood.
Conclusions: DSE behaviour remained a prominent, but largely clinically benign, young adult feature of some adoptees who experienced early deprivation.
The mechanistic target of the rapamycin (mTOR) inhibitor, temsirolimus, has significantly improved the outcome of patients with renal cell carcinoma (RCC). However, development of temsirolimus-resistance limits its effect and metastatic progression subsequently recurs. Since integrin α7 (ITGA7) is speculated to promote metastasis, this investigation was designed to investigate whether temsirolimus-resistance is associated with altered ITGA7 expression in RCC cell lines and modified tumor cell adhesion and invasion. Caki-1, KTCTL-26, and A498 RCC cell lines were driven to temsirolimus-resistance by exposing them to temsirolimus over a period of 12 months. Subsequently, adhesion to human umbilical vein endothelial cells, to immobilized fibronectin, or collagen was investigated. Chemotaxis was evaluated with a modified Boyden chamber assay and ITGA7 expression by flow cytometry and western blotting. Chemotaxis significantly decreased in temsirolimus-sensitive cell lines upon exposure to low-dosed temsirolimus, but increased in temsirolimus-resistant tumor cells upon reexposure to the same temsirolimus dose. The increase in chemotaxis was accompanied by elevated ITGA7 at the cell surface membrane with simultaneous reduction of intracellular ITGA7. ITGA7 knock-down significantly diminished motility of temsirolimous-sensitive cells but elevated chemotactic activity of temsirolimus-resistant Caki-1 and KTCTL-26 cells. Therefore, ITGA7 appears closely linked to adhesion and migration regulation in RCC cells. It is postulated that temsirolimus-resistance is associated with translocation of ITGA7 from inside the cell to the outer surface. This switch forces RCC migration forward. Whether ITGA7 can serve as an important target in combatting RCC requires further investigation.
Background: For prostate cancer treatment, treatment options with minimal side effects are desired. External beam radiation therapy (EBRT) is non-invasive, standard of care and delivered in either conventional fractionation over 8 weeks or with moderate hypo-fractionation over about 5 weeks. Recent advances in radiotherapy technology have made extreme hypo-fractionated stereotactic body radiation therapy (SBRT) of prostate cancer feasible, which has not yet been introduced as a standard treatment method in Germany. Initial results from other countries are promising, but long-term results are not yet available. The aim of this study is to investigate feasibility and effectiveness of SBRT for prostate cancer in Germany.
Methods/design: This German bi-center single group trial (HYPOSTAT) is designed to evaluate feasibility and effectiveness, as measured by toxicity and PSA-response, respectively, of an extreme hypo-fractionated SBRT regimen with five fractions of 7 Gy in treatment of localized low and intermediate risk prostate cancer. The target volume includes the prostate with or without the base of seminal vesicles depending on risk stratification and uncertainty margins that are kept at 3–5 mm. SBRT treatment is delivered with the robotic CyberKnife system, which was recently introduced in Germany. Acute and late toxicity after one year will be evaluated according to Common Terminology Criteria for Adverse Events (CTCAE v. 4.0), Radiation Therapy Oncology Group (RTOG) and International Prostate Symptom Score (IPSS) Scores. The quality of life will be assessed before and after treatment with the EORTC QLQ C30 questionnaire. Hypothesizing that the proportion of patients with grade 2 side effects or higher is less or equal than 2.8%, thus markedly lower than the standard EBRT percentage (17.5%), the recruitment target is 85 patients.
Discussion: The HYPOSTAT trial aims at demonstrating short term feasibility of extreme hypo-fractioned SBRT for the treatment of prostate cancer and might be used as the pilot study for a multi-center multi-platform or for randomized-controlled trials comparing conventional radiotherapy with SBRT for localized prostate cancer in the future. The study concept of patient enrollment, follow up and evaluation by multiple public university clinics and actual patient treatment in dedicated private radiosurgery practices with high-tech radiation equipment is unique for clinical trials.
Study status: The study is ongoing and currently recruiting patients.
Trial registration: Registration number: NCT02635256 (clinicaltrials.gov). Registered 8 December 2015
Natural Killer (NK) cells are involved in the host immune response against infections due to viral, bacterial and fungal pathogens, all of which are a significant cause of morbidity and mortality in immunocompromised patients. Since the recovery of the immune system has a major impact on the outcome of an infectious complication, there is major interest in strengthening the host response in immunocompromised patients, either by using cytokines or growth factors or by adoptive cellular therapies transfusing immune cells such as granulocytes or pathogen-specific T-cells. To date, relatively little is known about the potential of adoptively transferring NK cells in immunocompromised patients with infectious complications, although the anti-cancer property of NK cells is already being investigated in the clinical setting. This review will focus on the antimicrobial properties of NK cells and the current standing and future perspectives of generating and using NK cells as immunotherapy in patients with infectious complications, an approach which is promising and might have an important clinical impact in the future.
Early and adequate restoration of endothelial and tubular renal function is a substantial step during regeneration after ischemia reperfusion (IR) injury, occurring, e.g., in kidney transplantation, renal surgery, and sepsis. While tubular epithelial cell injury has long been of central importance, recent perception includes the renal vascular endothelium. In this regard, the fibrin cleavage product fibrinopeptide Bβ15-42 mitigate IR injury by stabilizing interendothelial junctions through its affinity to VE-cadherin. Therefore, this study focused on the effect of Bβ15-42 on post-acute physiological renal regeneration. For this, adult male C57BL/6 mice were exposed to a 30 min bilateral renal ischemia and reperfusion for 24 h or 48 h. Animals were randomized in a non-operative control group, two operative groups each treated with i.v. administration of either saline or Bβ15-42 (2.4 mg/kg) immediately prior to reperfusion. Endothelial activation and inflammatory response was attenuated in renal tissue homogenates by single application of Bβ15-42. Meanwhile, Bβ15-42 did not affect acute kidney injury markers. Regarding the angiogenetic players VEGF-A, Angiopoietin-1, Angiopoietin-2, however, we observed significant higher expressions at mRNA and trend to higher protein level in Bβ15-42 treated mice, compared to saline treated mice after 48 h of IR, thus pointing toward an increased angiogenetic activity. Similar dynamics were observed for the intermediate filament vimentin, the cytoprotective protein klotho, stathmin and the proliferation cellular nuclear antigen, which were significantly up-regulated at the same points in time. These results suggest a beneficial effect of anatomical contiguously located endothelial cells on tubular regeneration through stabilization of endothelial integrity. Therefore, it seems that Bβ15-42 represents a novel pharmacological approach in the targeted therapy of acute renal failure in everyday clinical practice.
Background: Root and tuber crops are a major food source in tropical Africa. Among these crops are several species in the monocotyledonous genus Dioscorea collectively known as yam, a staple tuber crop that contributes enormously to the subsistence and socio-cultural lives of millions of people, principally in West and Central Africa. Yam cultivation is constrained by several factors, and yam can be considered a neglected “orphan” crop that would benefit from crop improvement efforts. However, the lack of genetic and genomic tools has impeded the improvement of this staple crop.
Results: To accelerate marker-assisted breeding of yam, we performed genome analysis of white Guinea yam (Dioscorea rotundata) and assembled a 594-Mb genome, 76.4% of which was distributed among 21 linkage groups. In total, we predicted 26,198 genes. Phylogenetic analyses with 2381 conserved genes revealed that Dioscorea is a unique lineage of monocotyledons distinct from the Poales (rice), Arecales (palm), and Zingiberales (banana). The entire Dioscorea genus is characterized by the occurrence of separate male and female plants (dioecy), a feature that has limited efficient yam breeding. To infer the genetics of sex determination, we performed whole-genome resequencing of bulked segregants (quantitative trait locus sequencing [QTL-seq]) in F1 progeny segregating for male and female plants and identified a genomic region associated with female heterogametic (male = ZZ, female = ZW) sex determination. We further delineated the W locus and used it to develop a molecular marker for sex identification of Guinea yam plants at the seedling stage.
Conclusions: Guinea yam belongs to a unique and highly differentiated clade of monocotyledons. The genome analyses and sex-linked marker development performed in this study should greatly accelerate marker-assisted breeding of Guinea yam. In addition, our QTL-seq approach can be utilized in genetic studies of other outcrossing crops and organisms with highly heterozygous genomes. Genomic analysis of orphan crops such as yam promotes efforts to improve food security and the sustainability of tropical agriculture.
The myocyte enhancer factor 2 (MEF2) regulates transcription in cardiac myocytes and adverse remodeling of adult hearts. Activators of G protein‐coupled receptors (GPCRs) have been reported to activate MEF2, but a comprehensive analysis of GPCR activators that regulate MEF2 has to our knowledge not been performed. Here, we tested several GPCR agonists regarding their ability to activate a MEF2 reporter in neonatal rat ventricular myocytes. The inflammatory mediator prostaglandin E2 (PGE2) strongly activated MEF2. Using pharmacological and protein‐based inhibitors, we demonstrated that PGE2 regulates MEF2 via the EP3 receptor, the βγ subunit of Gi/o protein and two concomitantly activated downstream pathways. The first consists of Tiam1, Rac1, and its effector p21‐activated kinase 2, the second of protein kinase D. Both pathways converge on and inactivate histone deacetylase 5 (HDAC5) and thereby de‐repress MEF2. In vivo, endotoxemia in MEF2‐reporter mice induced upregulation of PGE2 and MEF2 activation. Our findings provide an unexpected new link between inflammation and cardiac remodeling by de‐repression of MEF2 through HDAC5 inactivation, which has potential implications for new strategies to treat inflammatory cardiomyopathies.
Recent experiments have demonstrated that visual cortex engages in spatio-temporal sequence learning and prediction. The cellular basis of this learning remains unclear, however. Here we present a spiking neural network model that explains a recent study on sequence learning in the primary visual cortex of rats. The model posits that the sequence learning and prediction abilities of cortical circuits result from the interaction of spike-timing dependent plasticity (STDP) and homeostatic plasticity mechanisms. It also reproduces changes in stimulus-evoked multi-unit activity during learning. Furthermore, it makes precise predictions regarding how training shapes network connectivity to establish its prediction ability. Finally, it predicts that the adapted connectivity gives rise to systematic changes in spontaneous network activity. Taken together, our model establishes a new conceptual bridge between the structure and function of cortical circuits in the context of sequence learning and prediction.
Im Rahmen eines Artenhilfsprogramms der Botanischen Vereinigung für Naturschutz in Hessen wurde im Jahr 2012 eine Untersuchung zur Bestandssituation der in Hessen vom Aussterben bedrohten Saum-Segge (Carex hostiana) durchgeführt. Betrachtet man die bis in das Jahr 1798 zurückreichenden Literaturquellen und Herbarbelege, lassen sich über einen Zeitraum von mehr als 200 Jahren für 38 hessische TK25-Viertelquadranten Funde von Carex hostiana belegen. Aktuell kommt die Art nur noch in sechs TK25-Viertelquadranten vor, wobei in diesen 12 Populationen unterschieden werden können. Nach den durchgeführten Untersuchungen kann der Gesamtbestand der Saum-Segge in Hessen auf etwa 85000 Individuen geschätzt werden, wobei die besiedelte Fläche nur 2,76 ha beträgt. Die Schwerpunkte der Vorkommen liegen im Taunus und im Messeler Hügelland. Zu den erfassten Populationen werden pflanzensoziologische Aufnahmen präsentiert sowie Aussagen zum Erhaltungszustand und zu möglichen Schutz- und Entwicklungsmaßnahmen getroffen.
Within the scope of the Wildlife Conservation Programme of the Botanical Society for the Nature Conservation in Hesse, a comprehensive survey was carried out of a comparatively common species, the Common Pasque Flower (Pulsatilla vulgaris). It still occurs in large populations on the nutrient poor chalk meadows of the Vorderhoen and Kuppenhoen. Other populations are known from the Wetterau and the Schluechterner Becken. A few other populations are known, but they only have a few individuals. Altogether 64 populations were recorded, five with more than 1,000 plants. The largest population, with over 50,000 individuals, is in the Weinberg nature reserve, Molzbach (near Huenfeld).
Verwilderte Vorkommen von als Zierpflanzen genutzten Frühblühern wurden im Frühjahr 2012 auf 13 ausgewählten Frankfurter Friedhöfen untersucht. Dabei wurde auf eine gleichmäßige Verteilung der Untersuchungsflächen im Stadtgebiet genauso geachtet wie auf eine hohe Vielfalt an Friedhofstypen. Auf circa 155 ha Fläche wurden 46 Arten gefunden. Dabei ist die Artenzahl der untersuchten Artengruppe auf größeren, extensiv bewirtschafteten Friedhöfen deutlich höher als auf kleinen, intensiver gepflegten Anlagen. Dagegen konnte zwischen Artenzahl und Alter der Friedhöfe keine Korrelation nachgewiesen werden. Große, alte und extensiv bewirtschaftete Friedhöfe stellen einen Rückzugsort für urbanophobe Pflanzenarten dar, weil auf ihnen der anthropogene Einfluss geringer ist als im übrigen Stadtgebiet.
Die Vorkommen des Haarstrang-Wasserfenchels (Oenanthe peucedanifolia) wurden bei einer umfassenden Bestandsaufnahme der ehemaligen und aktuellen hessischen Nachweise erfaßt. Im Taunus und im Messeler Hügelland konnten zum Teil sehr individuenreiche Bestände gefunden werden. Dennoch gehört der Haarstrang- Wasserfenchel unter Berücksichtigung der noch in der jüngeren Vergangenheit verlorenen Wuchsorte zu den gefährdeten Pflanzenarten Hessens, für die es notwendig ist zum Überleben geeignete Schutz- und Erhaltungsmaßnahmen durchzuführen.
Seit dem Erscheinen der als Beiheft 11 publizierten "Letzten Nachweise der in Hessen ausgestorbenen oder verschollenen Pflanzenarten" konnten weitere Angaben zu ehemaligen Vorkommen in Hessen durch Auswertung von gedruckten Quellen und Sichtung von Herbarbelegen gewonnen werden. Für sechs Arten – Blackstonia acuminata, Illecebrum verticillatum, Laserpitium prutenicum, Luronium natans, Utricularia intermedia, Wolffia arrhiza – ließ sich ein jüngeres Datum des letzten Nachweises ermitteln. Zwei Arten, Bromus grossus und Cyperus flavescens, wurden in jüngster Zeit wieder in Hessen aufgefunden und können damit nicht mehr als verschollen gelten. Außerdem ergeben sich Erstnachweise für zwei Regionen und Angaben für Vorkommen auf 26 bislang nicht genannten TK-Quadranten.
Das im Gotischen Haus in Bad Homburg vor der Höhe aufbewahrte Herbarium des Geologen Friedrich Rolle (1827–1887) wurde gesichtet. Die von uns als Wildpflanzen klassifizierten Arten wurden nachbestimmt und alphabetisch mit den Fundortangaben aufgelistet. In der Auswertung unberücksichtigt blieben in der Sammlung vorhandene Kulturpflanzen und Belege aus dem Botanischen Garten Darmstadt. Die meisten Belege der Sammlung stammen aus der näheren Umgebung von Darmstadt und aus dem angrenzenden Odenwald sowie aus der Umgebung von Bad Homburg vor der Höhe. Auf bemerkenswerte Belege von Arten, die wegen ihres starken Rückgangs in der aktuellen Flora Hessens sehr selten geworden sind oder inzwischen ganz fehlen, wird eingegangen, zum Beispiel: Herminium monorchis, Liparis loeselii, Moenchia erecta, Orchis palustris und Tofieldia calyculata. Für Rheinland-Pfalz ist der Beleg der ausgestorbenen Androsace maxima hervorzuheben. Zur besseren Verwertung der Daten wurden die Fundorte den Messtischblatt-Qudranten zugeordnet.
Die Verbreitung von Carex hordeistichos in Hessen wurde während der Jahre 1999 bis 2012 untersucht. Die Art war aus 7 Fundgebieten in der Wetterau (4), dem Main-Taunus-Vorland (1), der Hessischen Rheinebene (1) und dem Vorderen Odenwald (1) bekannt. Nur die Population in der Wetterau bei Nieder-Wöllstadt besteht noch, 2012 war sie auf 1 Pflanze reduziert. Die übrigen Vorkommen sind seit über hundert Jahren verschollen und konnten nicht bestätigt werden. Möglichkeiten, die Art in Hessen vor dem Aussterben zu bewahren, werden diskutiert. Die Naturschutzbehörde des Wetteraukreises ist seit 1997 bemüht, im Rahmen eines Artenhilfsprogramms die existente Population zu stärken und neue aufzubauen.