Establishment of a Human Blood-Brain Barrier Co-culture Model Mimicking the Neurovascular Unit Using Induced Pluri- and Multipotent Stem Cells

Summary In vitro models of the human blood-brain barrier (BBB) are highly desirable for drug development. This study aims to analyze a set of ten different BBB culture models based on primary cells, human induced pluripotent stem cells (hiPSCs), and multipotent fetal neural stem cells (fNSCs). We systematically investigated the impact of astrocytes, pericytes, and NSCs on hiPSC-derived BBB endothelial cell function and gene expression. The quadruple culture models, based on these four cell types, achieved BBB characteristics including transendothelial electrical resistance (TEER) up to 2,500 Ω cm2 and distinct upregulation of typical BBB genes. A complex in vivo-like tight junction (TJ) network was detected by freeze-fracture and transmission electron microscopy. Treatment with claudin-specific TJ modulators caused TEER decrease, confirming the relevant role of claudin subtypes for paracellular tightness. Drug permeability tests with reference substances were performed and confirmed the suitability of the models for drug transport studies

Oxygen fluxes beneath Arctic land-fast ice and pack ice: towards estimates of ice productivity

Sea-ice ecosystems are among the most extensive of Earth's habitats; yet its autotrophic and heterotrophic activities remain poorly constrained. We employed the in situ aquatic eddy-covariance (AEC) O-2 flux method and laboratory incubation techniques ((HCO3-)-C-14, [H-3] thymidine and [H-3] leucine) to assess productivity in Arctic sea-ice using different methods, in conditions ranging from land-fast ice during winter, to pack ice within the central Arctic Ocean during summer. Laboratory tracer measurements resolved rates of bacterial C demand of 0.003-0.166mmolCm(-2)day(-1) and primary productivity rates of 0.008-0.125mmolCm(-2)day(-1) for the different ice floes. Pack ice in the central Arctic Ocean was overall net autotrophic (0.002-0.063mmolCm(-2)day(-1)), whereas winter land-fast ice was net heterotrophic (-0.155mmol C m(-2) day(-1)). AEC measurements resolved an uptake of O-2 by the bottom-ice environment, from similar to-2mmolO(2)m(-2) day(-1) under winter land-fast ice to similar to-6mmolO(2)m(-2)day(-1) under summer pack ice. Flux of O-2-deplete meltwater and changes in water flow velocity masked potential biological-mediated activity. AEC estimates of primary productivity were only possible at one study location. Here, productivity rates of 1.3 +/- 0.9mmolO(2)m(-2)day(-1), much larger than concurrent laboratory tracer estimates (0.03mmolCm(-2)day(-1)), indicate that ice algal production and its importance within the marine Arctic could be underestimated using traditional approaches. Given careful flux interpretation and with further development, the AEC technique represents a promising new tool for assessing oxygen dynamics and sea-ice productivity in ice-covered regions.Peer reviewe

Sirenengesänge. Neun Bamberger Vorträge zu Libretto und Musiktheater

Im Sommersemester 2015 am Institut für Romanistik der Universität Bamberg eine Reihe von acht Vorträgen zum (Opern- und Operetten)Libretto und zum Musiktheater statt. Behandelt wurden die Unterschiede zwischen deutscher und französischer Operette; Exotismus im (italienischen und frnazösischen) Musiktheater des 17. und 18. Jahrhunderts; Offenbach und sein Werk in der zeitgenössischen Karikatur; neue Formen des Erzählens im Musiktheater der Gegenwart; die Künstleroper; Probleme bei der Übersetzung von Barocklibretti; Mozarts Librettisten; das Verhältnis von Text, Musik und Inszenierung in Musiktheater und Chanson. Am Ende steht die Abschiedsvorlesung ders Herausgebers zu den Sirenen in Literatur und Musiktheater.During the summer half 2016, a series of 6 lectures about the libretto in opera and operetta took place at the Institut für Romanistik of Bamberg Universtiy. They dealt with the differences between French and German operetta; exoticism in the opera of the 17th / 18th centuries; Jacques Offenbach and his theatre in contemporary caricatures; new types of narrative in the opera today; the "Künstleroper"; how to translate Italian opera librettos of the 17th century; Mozart's librettists; the interrelations between text, music, and scene in opera and song. The volume is closed by the farewell lecture of the editor Albert Gier about the sirens in literature and opera

High statistics study of the reaction γp→p 2π0\gamma p\to p\;2\pi^0

The photoproduction of 2$\pi^0$ mesons off protons was studied with the Crystal Barrel/TAPS experiment at the electron accelerator ELSA in Bonn. The energy of photons produced in a radiator was tagged in the energy range from 600\,MeV to 2.5\,GeV. Differential and total cross sections and $p\pi^0\pi^0$ Dalitz plots are presented. Part of the data was taken with a diamond radiator producing linearly polarized photons, and beam asymmetries were derived. Properties of nucleon and $\Delta$ resonances contributing to the $p\pi^0\pi^0$ final state were determined within the BnGa partial wave analysis. The data presented here allow us to determine branching ratios of nucleon and $\Delta$ resonances for their decays into $p\pi^0\pi^0$ via several intermediate states. Most prominent are decays proceeding via $\Delta(1232)\pi$, $N(1440)1/2^+\pi$, $N(1520)3/2^-\pi$, $N(1680)5/2^+\pi$, but also $pf_0(500)$, $pf_0(980)$, and $pf_2(1270)$ contribute to the reaction.Comment: 28 pages, 17 figures, 7 table

Photoproduction of meson pairs: First measurement of the polarization observable I^s

The polarization observable I^s, a feature exclusive to the acoplanar kinematics of multi-meson final states produced via linearly polarized photons, has been measured for the first time. Results for the reaction g p -> p pi0 eta are presented for incoming photon energies between 970 MeV and 1650 MeV along with the beam asymmetry I^c. The comparably large asymmetries demonstrate a high sensitivity of I^s to the dynamics of the reaction. Fits using Bonn-Gatchina partial wave analysis demonstrate that the new polarization observables carry significant information on the contributing partial waves.Comment: 11 pages, 6 figures, v2 to appear in Phys. Lett.

Göttliche, menschliche und teuflische Komödien - Europäische Welttheater-Entwürfe im 19. und 20. Jahrhundert

Theater kann nicht nur Welt abbilden, sondern auch die Welt selbst als ein Theater darstellen, in dem Gott (oder das Schicksal) die Rollen verteilt und Regie führt. So wurde 'Welttheater' im europäischen Barock aufgefasst. Seit der Aufklärung schwindet der Glaube an den göttlichen Regisseur, die Denkfigur 'Welttheater' behält aber auch im 19. und 20. Jahrhundert ihre Attraktivität. Im Rahmen einer Ringvorlesung an der Fakultät Geistes- und Kulturwissenschaften der Otto-Friedrich-Universität Bamberg im Wintersemester 2009/2010 wurden dreizehn Beispiele modernen Welttheaters aus Sprech- und Musiktheater Frankreichs, Italiens, Ungarns, Rußlands und Deutschlands vorgestellt (mit Ausblicken zu Film und Fernsehen), von Goethes Faust über Wagners Ring des Nibelungen, Imre Madàchs Tragödie des Menschen, Hofmannsthals Großes Salzburger Welttheater oder Paul Claudels Seidenen Schuh bis hin zu Tankred Dorsts Merlin und Karlheinz Stockausens LICHT-Zyklus. Den Abschluss bildet ein Werkstattgespräch mit dem Komponisten Peter Eötvös und seinem Librettisten Albert Ostermaier, deren Oper Die Tragödie des Teufels im Februar 2010 in München uraufgeführt wurde

Long-Term Summertime Investigations of Pelagic and Benthic Realms with Continuous Observations of Vertical Particle Flux in the Fram Strait and the Central Arctic Ocean

Sea ice volume and extent currently experience massive reduction in the Arctic Ocean due to climate change. Our long-term study aims at tracing effects of environmental changes in pelagic and benthic systems and investigate accompanying impacts on the fate of organic matter produced in the upper water column on its way down to the seafloor. Since the start of our observations in 1999, we have already seen some effects and will present selected data sets from the upper water column and benthic data during summer expeditions as well as results from vertical particle flux measurements that were obtained from annually deployed sediment traps at the LTER (Long-Term Ecological Research) observatory HAUSGARTEN in the eastern Fram Strait (79°/4°E) and on fewer occasions in the central Arctic Ocean (CAO). Highest biomass was found in the eastern Fram Strait and lowest in the heavily ice-covered regions in the CAO. Flux rates of POC where at least one order of magnitude lower in the CAO than in the eastern Fram Strait. While in the CAO ice algae dominate the recognizable flux fraction, faecal material prevailed in eastern Fram Strait traps. This points towards different systems of organic matter production and modification and, thus, different mechanisms determine the efficiency of the biological carbon pump. These differences are also reflected in the benthic communities in the CAO and in the eastern Fram Strait. These first results have shown the importance of long-term observations and encouraged the continuation of the Arctic Ocean Observing System FRAM (FRontiers in Arctic marine Monitoring) to record environmental and biological data at high temporal and spatial resolution

Mergers in Lambda-CDM: Uncertainties in Theoretical Predictions and Interpretations of the Merger Rate

Different methodologies lead to order-of-magnitude variations in predicted galaxy merger rates. We examine and quantify the dominant uncertainties. Different halo merger rates and subhalo 'destruction' rates agree to within a factor ~2 given proper care in definitions. If however (sub)halo masses are not appropriately defined or are under-resolved, the major merger rate can be dramatically suppressed. The dominant differences in galaxy merger rates owe to baryonic physics. Hydrodynamic simulations without feedback and older models that do not agree with the observed galaxy mass function propagate factor ~5 bias in the resulting merger rates. However, if the model matches the galaxy mass function, properties of central galaxies are sufficiently converged to give small differences in merger rates. But variations in baryonic physics of satellites also have dramatic effects. The known problem of satellite 'over-quenching' in most semi-analytic models (SAMs), whereby SAM satellites are too efficiently stripped of gas, could lead to order-of-magnitude under-estimates of merger rates for low-mass, gas-rich galaxies. Fixing the satellite properties to observations tends to predict higher merger rates, but with factor ~2 empirical uncertainties. Choice of mass ratio definition matters: at low masses, most true major mergers (in baryonic/dynamical galaxy mass) will appear to be minor mergers in their stellar or luminosity mass ratio. Observations and models using these criteria may underestimate major merger rates by factors ~5. Orbital parameters and gas fractions also introduce factor ~3 differences in amount of bulge formed by mergers, even for fixed mass ratio encounters.Comment: 32 Pages, 15 figures, accepted to ApJ (revised to match accepted version and correct Fig. 12

The dynamic cilium in human diseases

Cilia are specialized organelles protruding from the cell surface of almost all mammalian cells. They consist of a basal body, composed of two centrioles, and a protruding body, named the axoneme. Although the basic structure of all cilia is the same, numerous differences emerge in different cell types, suggesting diverse functions. In recent years many studies have elucidated the function of 9+0 primary cilia. The primary cilium acts as an antenna for the cell, and several important pathways such as Hedgehog, Wnt and planar cell polarity (PCP) are transduced through it. Many studies on animal models have revealed that during embryogenesis the primary cilium has an essential role in defining the correct patterning of the body. Cilia are composed of hundreds of proteins and the impairment or dysfunction of one protein alone can cause complete loss of cilia or the formation of abnormal cilia. Mutations in ciliary proteins cause ciliopathies which can affect many organs at different levels of severity and are characterized by a wide spectrum of phenotypes. Ciliary proteins can be mutated in more than one ciliopathy, suggesting an interaction between proteins. To date, little is known about the role of primary cilia in adult life and it is tempting to speculate about their role in the maintenance of adult organs. The state of the art in primary cilia studies reveals a very intricate role. Analysis of cilia-related pathways and of the different clinical phenotypes of ciliopathies helps to shed light on the function of these sophisticated organelles. The aim of this review is to evaluate the recent advances in cilia function and the molecular mechanisms at the basis of their activity