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Online-Ausg. der autographen Notenhs. von Engelbert Humperdinck (Signatur: Mus Hs 2141) der Universitätsbibliothek Johann Christian Senckenberg Frankfurt am Main Enth.: Vorspiel. Das Heiltum. Am Waldsee. Einzug in die Gralsburg und Liebesmahlscene. Klingsor's Zauberschloss. Klingsor's Zaubergarten. Einleitung. Finale (Charfreitag) Einheitssachtitel: Parsifal / Ausw. Arr.
Colorectal carcinoma (CRC) is a major cause of morbidity and mortality in Western countries. It has so far been molecularly defined mainly by alterations of the Wnt pathway. We show here for the first time that aberrant activities of the signal transducer and activator of transcription STAT3 actively contribute to this malignancy and, thus, are a potential therapeutic target for CRC. Constitutive STAT3 activity was found to be abundant in dedifferentiated cancer cells and infiltrating lymphocytes of CRC samples, but not in non-neoplastic colon epithelium. Cell lines derived from malignant colorectal tumors lost persistent STAT3 activity in culture. However, implantation of colon carcinoma cells into nude mice resulted in restoration of STAT3 activity, suggesting a role of an extracellular stimulus within the tumor microenvironment as a trigger for STAT activation. STAT3 activity in CRC cells triggered through interleukin-6 or through a constitutively active STAT3 mutant promoted cancer cell multiplication, whereas STAT3 inhibition through a dominant-negative variant impaired IL-6-driven proliferation. Blockade of STAT3 activation in CRCderived xenograft tumors slowed down their development, arguing for a contribution of STAT3 to colorectal tumor growth.
k-MED entwickelte sich von einem fachbezogenen Projekt im Jahr 1999 zu einem e-Learning-Dienstleister mit umfangreichen Lehr-Lernangeboten sowie einer technischen und organisatorischen Infrastruktur für Autoren und Nutzer. Es bietet heute – Mitte 2006 – 5000 Studierenden, v.a. der Humanmedizin, ca. 170 Lernkurse aus 16 medizinischen Fächern. Das Projekt umfasst erfahrenes Fachpersonal und nutzt eine eigene Online-Autorenumgebung sowie eine internetbasierte Lernplattform, deren Funktionalitäten in Abstimmung mit evaluierten Lehr- und Lern-Szenarien ständig weiter entwickelt werden. Die wichtigste Aufgabe ist die Vollversorgung von Bildungseinrichtungen, darunter vor allem medizinische Fakultäten, mit Lehr-Lern- und Kommunikationsinstrumenten. Aktuelle Informationen sind zu finden unter http://www.k-med.org.
Bacterial porin disrupts mitochondrial membrane potential and sensitizes host cells to apoptosis
(2009)
The bacterial PorB porin, an ATP-binding beta-barrel protein of pathogenic Neisseria gonorrhoeae, triggers host cell apoptosis by an unknown mechanism. PorB is targeted to and imported by host cell mitochondria, causing the breakdown of the mitochondrial membrane potential (delta psi m). Here, we show that PorB induces the condensation of the mitochondrial matrix and the loss of cristae structures, sensitizing cells to the induction of apoptosis via signaling pathways activated by BH3-only proteins. PorB is imported into mitochondria through the general translocase TOM but, unexpectedly, is not recognized by the SAM sorting machinery, usually required for the assembly of beta-barrel proteins in the mitochondrial outer membrane. PorB integrates into the mitochondrial inner membrane, leading to the breakdown of delta psi m. The PorB channel is regulated by nucleotides and an isogenic PorB mutant defective in ATP-binding failed to induce delta psi m loss and apoptosis, demonstrating that dissipation of delta psi m is a requirement for cell death caused by neisserial infection.
The ALICE Collaboration has made the first measurement at the LHC of J/ψ photoproduction in ultra-peripheral Pb–Pb collisions at sNN=2.76 TeV. The J/ψ is identified via its dimuon decay in the forward rapidity region with the muon spectrometer for events where the hadronic activity is required to be minimal. The analysis is based on an event sample corresponding to an integrated luminosity of about 55 μb−1. The cross section for coherent J/ψ production in the rapidity interval −3.6<y<−2.6 is measured to be dσJ/ψcoh/dy=1.00±0.18(stat)−0.26+0.24(syst) mb. The result is compared to theoretical models for coherent J/ψ production and found to be in good agreement with those models which include nuclear gluon shadowing.
A measurement of the multi-strange Ξ− and Ω− baryons and their antiparticles by the ALICE experiment at the CERN Large Hadron Collider (LHC) is presented for inelastic proton–proton collisions at a centre-of-mass energy of 7 TeV. The transverse momentum (pT) distributions were studied at mid-rapidity (|y|<0.5) in the range of 0.6<pT<8.5 GeV/c for Ξ− and Ξ¯+ baryons, and in the range of 0.8<pT<5 GeV/c for Ω− and Ω¯+. Baryons and antibaryons were measured as separate particles and we find that the baryon to antibaryon ratio of both particle species is consistent with unity over the entire range of the measurement. The statistical precision of the current data has allowed us to measure a difference between the mean pT of Ξ− (Ξ¯+) and Ω− (Ω¯+). Particle yields, mean pT, and the spectra in the intermediate pT range are not well described by the PYTHIA Perugia 2011 tune Monte Carlo event generator, which has been tuned to reproduce the early LHC data. The discrepancy is largest for Ω− (Ω¯+). This PYTHIA tune approaches the pT spectra of Ξ− and Ξ¯+ baryons below pT<0.85 GeV/c and describes the Ξ− and Ξ¯+ spectra above pT>6.0 GeV/c. We also illustrate the difference between the experimental data and model by comparing the corresponding ratios of (Ω−+Ω¯+)/(Ξ−+Ξ¯+) as a function of transverse mass.
Identical neutral kaon pair correlations are measured in √s=7 TeV pp collisions in the ALICE experiment. One-dimensional Ks0Ks0 correlation functions in terms of the invariant momentum difference of kaon pairs are formed in two multiplicity and two transverse momentum ranges. The femtoscopic parameters for the radius and correlation strength of the kaon source are extracted. The fit includes quantum statistics and final-state interactions of the a0/f0 resonance. Ks0Ks0 correlations show an increase in radius for increasing multiplicity and a slight decrease in radius for increasing transverse mass, mT, as seen in ππ correlations in pp collisions and in heavy-ion collisions. Transverse mass scaling is observed between the Ks0Ks0 and ππ radii. Also, the first observation is made of the decay of the f2′(1525) meson into the Ks0Ks0 channel in pp collisions.
The pT-differential inclusive production cross section of the prompt charm-strange meson Ds+ in the rapidity range |y|<0.5 was measured in proton–proton collisions at s=7 TeV at the LHC using the ALICE detector. The analysis was performed on a data sample of 2.98×108 events collected with a minimum-bias trigger. The corresponding integrated luminosity is Lint=4.8 nb−1. Reconstructing the decay Ds+→ϕπ+, with ϕ→K−K+, and its charge conjugate, about 480 Ds± mesons were counted, after selection cuts, in the transverse momentum range 2<pT<12 GeV/c. The results are compared with predictions from models based on perturbative QCD. The ratios of the cross sections of four D meson species (namely D0, D+, D⁎+ and Ds+) were determined both as a function of pT and integrated over pT after extrapolating to full pT range, together with the strangeness suppression factor in charm fragmentation. The obtained values are found to be compatible within uncertainties with those measured by other experiments in e+e−, ep and pp interactions at various centre-of-mass energies.
Nucleation of aerosol particles from trace atmospheric vapours is thought to provide up to half of global cloud condensation nuclei. Aerosols can cause a net cooling of climate by scattering sunlight and by leading to smaller but more numerous cloud droplets, which makes clouds brighter and extends their lifetimes. Atmospheric aerosols derived from human activities are thought to have compensated for a large fraction of the warming caused by greenhouse gases. However, despite its importance for climate, atmospheric nucleation is poorly understood. Recently, it has been shown that sulphuric acid and ammonia cannot explain particle formation rates observed in the lower atmosphere. It is thought that amines may enhance nucleation, but until now there has been no direct evidence for amine ternary nucleation under atmospheric conditions. Here we use the CLOUD (Cosmics Leaving Outdoor Droplets) chamber at CERN and find that dimethylamine above three parts per trillion by volume can enhance particle formation rates more than 1,000-fold compared with ammonia, sufficient to account for the particle formation rates observed in the atmosphere. Molecular analysis of the clusters reveals that the faster nucleation is explained by a base-stabilization mechanism involving acid–amine pairs, which strongly decrease evaporation. The ion-induced contribution is generally small, reflecting the high stability of sulphuric acid–dimethylamine clusters and indicating that galactic cosmic rays exert only a small influence on their formation, except at low overall formation rates. Our experimental measurements are well reproduced by a dynamical model based on quantum chemical calculations of binding energies of molecular clusters, without any fitted parameters. These results show that, in regions of the atmosphere near amine sources, both amines and sulphur dioxide should be considered when assessing the impact of anthropogenic activities on particle formation.