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The mitophagy receptor Nix interacts with LC3/GABARAP proteins, targeting mitochondria into autophagosomes for degradation. Here we present evidence for phosphorylation-driven regulation of the Nix:LC3B interaction. Isothermal titration calorimetry and NMR indicate a ~100 fold enhanced affinity of the serine 34/35-phosphorylated Nix LC3-interacting region (LIR) to LC3B and formation of a very rigid complex compared to the non-phosphorylated sequence. Moreover, the crystal structure of LC3B in complex with the Nix LIR peptide containing glutamic acids as phosphomimetic residues and NMR experiments revealed that LIR phosphorylation stabilizes the Nix:LC3B complex via formation of two additional hydrogen bonds between phosphorylated serines of Nix LIR and Arg11, Lys49 and Lys51 in LC3B. Substitution of Lys51 to Ala in LC3B abrogates binding of a phosphomimetic Nix mutant. Functionally, serine 34/35 phosphorylation enhances autophagosome recruitment to mitochondria in HeLa cells. Together, this study provides cellular, biochemical and biophysical evidence that phosphorylation of the LIR domain of Nix enhances mitophagy receptor engagement.
In der heutigen Epoche von Radikalismen, politischer und existentieller Unbehaustheit und vermeintlich in die Krise geratener Männlichkeit wird die "vaterlose Gesellschaft" (Matthias Matussek) oft als Ursache für vielfache Fehlentwicklungen insbesondere der Söhne betrachtet und geradezu zur conditio humana der westlichen Welt erklärt. Zwar wird diese 'Vaterlosigkeit' vor allem im rechtskonservativen Lager immer wieder als Verlustgeschichte natürlicher männlicher Vorherrschaft bedauert, aber auch ein kritisch-engagierter Autor wie Milo Rau scheint in seinem Theaterstück Civil Wars ein (Ideal-)Bild normal-autoritärer väterlicher Männlichkeit zu vermitteln, insofern besonders das problematische Verhältnis zum Vater das Stück leitmotivisch durchzieht und als Ursache für die psychosoziale Fehlentwicklung der Figuren aufgeführt wird.
Um 1900 wurde diese heute so oft beklagte vaterlose Gesellschaft aber geradezu herbeigesehnt: Nicht nur die eben erst gegründete bürgerliche Jugendbewegung, sondern auch die reformwillige wilhelminische Elternschaft, die im morbiden Aufbruch der (männlichen) Jugend ihre eigenen politischen Hoffnungen zu realisieren wünschte, erhoben den Vatermord provokativ zum Teil ihres Programms.
Mit dem Ziel einer Re-Politisierung der Selbstbildung im Sinne einer politischen Ökologie legt Katja Rothe das Spiel als ein Gefüge aus, welches das Subjekt auf eine "umweltliche" Weise herstellt, mit sozialen Formen verbindet und kontextualisiert. Ausgehend von einem Überblick über die Bedeutung des Spiels und der Spieltherapien in der psychologischen Praxis von Hermine Hug-Hellmuth über Anna Freud und Melanie Klein, Margaret Lowenfeld und Dora Kalff und deren Vernachlässigung in der Wissenschaftsgeschichte der Psychologie schlägt Rothe vor, Spiele als Formen und Technologien der "Selbst-Bildung" auszulegen, in denen die Interaktion mit Objekten den Ausgangspunkt von offenen bedeutungsgenerierenden Prozessen bildet. Dabei bezieht sich Rothe, wenn sie von Objekten spricht, auf das Konzept des Übergangsobjekts, das im Zentrum von Winnicotts Theorie des Spiels steht. Das zu einem Ort des Übergangs gewordene Objekt beschreibt sie als jenes Element im Spiel, das es erlaubt, etwas zu finden, was man erfunden habe. Das Spiel wird damit als Versammlungsort beschreibbar, an dem sich Subjekt und Objekt in umweltlicher Weise gegenseitig konstituieren.
We investigate the effect of large magnetic fields on the (2 + 1)-dimensional reduced-magnetohydrodynamical expansion of hot and dense nuclear matter produced in √sNN = 200 GeV Au+Au collisions. For the sake of simplicity,we consider the casewhere themagnetic field points in the direction perpendicular to the reaction plane. We also consider this field to be external, with energy density parametrized as a two-dimensional Gaussian. The width of the Gaussian along the directions orthogonal to the beam axis varies with the centrality of the collision. The dependence of the magnetic field on proper time (τ ) for the case of zero electrical conductivity of the QGP is parametrized following Deng et al. [Phys. Rev. C 85, 044907 (2012)], and for finite electrical conductivity following Tuchin [Phys. Rev. C 88, 024911 (2013)].We solve the equations of motion of ideal hydrodynamics for such an external magnetic field. For collisions with nonzero impact parameter we observe considerable changes in the evolution of the momentum eccentricities of the fireball when comparing the case when the magnetic field decays in a conducting QGP medium and when no magnetic field is present. The elliptic-flow coefficient v2 of π− is shown to increase in the presence of an external magnetic field and the increment in v2 is found to depend on the evolution and the initial magnitude of the magnetic field.
Denisovite is a rare mineral occurring as aggregates of fibres typically 200–500 nm diameter. It was confirmed as a new mineral in 1984, but important facts about its chemical formula, lattice parameters, symmetry and structure have remained incompletely known since then. Recently obtained results from studies using microprobe analysis, X-ray powder diffraction (XRPD), electron crystallography, modelling and Rietveld refinement will be reported. The electron crystallography methods include transmission electron microscopy (TEM), selected-area electron diffraction (SAED), high-angle annular dark-field imaging (HAADF), high-resolution transmission electron microscopy (HRTEM), precession electron diffraction (PED) and electron diffraction tomography (EDT). A structural model of denisovite was developed from HAADF images and later completed on the basis of quasi-kinematic EDT data by ab initio structure solution using direct methods and least-squares refinement. The model was confirmed by Rietveld refinement. The lattice parameters are a = 31.024 (1), b = 19.554 (1) and c = 7.1441 (5) Å, β = 95.99 (3)°, V = 4310.1 (5) Å3 and space group P12/a1. The structure consists of three topologically distinct dreier silicate chains, viz. two xonotlite-like dreier double chains, [Si6O17]10−, and a tubular loop-branched dreier triple chain, [Si12O30]12−. The silicate chains occur between three walls of edge-sharing (Ca,Na) octahedra. The chains of silicate tetrahedra and the octahedra walls extend parallel to the z axis and form a layer parallel to (100). Water molecules and K+ cations are located at the centre of the tubular silicate chain. The latter also occupy positions close to the centres of eight-membered rings in the silicate chains. The silicate chains are geometrically constrained by neighbouring octahedra walls and present an ambiguity with respect to their z position along these walls, with displacements between neighbouring layers being either Δz = c/4 or −c/4. Such behaviour is typical for polytypic sequences and leads to disorder along [100]. In fact, the diffraction pattern does not show any sharp reflections with l odd, but continuous diffuse streaks parallel to a* instead. Only reflections with l even are sharp. The diffuse scattering is caused by (100) nanolamellae separated by stacking faults and twin boundaries. The structure can be described according to the order–disorder (OD) theory as a stacking of layers parallel to (100).
In our “House Europe” the exchange of ideas is going on intensively and the multi-cultural societies are in continuous transformation. An interesting example for cultural transfer in a multi-lingual and multi-confessional society is the reception of the St. Martin’s Day combined with the lantern procession organized by the German schools in Transylvania. The schools with German teaching language in Romania became a practice area for intercultural communication. Since 1997, first grade students at German schools in Romania learn from a new reading primer. One of the reading passages, “Our Lantern Festival”, initiated the spreading of a feast which had not been popular before neither with the German speaking minority of the Transylvanian Saxons, nor with the Romanian majority. The Lantern Festival is closely linked to the celebration of St. Martin, who is a European figure of high symbolic power. We can allege that the cultural diversity is an additional value for Europe. In the era of globalization, when migration processes and cultural hybridization are getting more intense, the intercultural communication has to adjust its inherited paradigm to the contemporary dynamics and heterogeneity of cultures.
Local treatment of unresectable colorectal liver metastases : results of a randomized phase II trial
(2017)
Background: Tumor ablation is often employed for unresectable colorectal liver metastases. However, no survival benefit has ever been demonstrated in prospective randomized studies. Here, we investigate the long-term benefits of such an aggressive approach.
Methods: In this randomized phase II trial, 119 patients with unresectable colorectal liver metastases (n < 10 and no extrahepatic disease) received systemic treatment alone or systemic treatment plus aggressive local treatment by radiofrequency ablation ± resection. Previously, we reported that the primary end point (30-month overall survival [OS] > 38%) was met. We now report on long-term OS results. All statistical tests were two-sided. The analyses were according to intention to treat.
Results: At a median follow up of 9.7 years, 92 of 119 (77.3%) patients had died: 39 of 60 (65.0%) in the combined modality arm and 53 of 59 (89.8%) in the systemic treatment arm. Almost all patients died of progressive disease (35 patients in the combined modality arm, 49 patients in the systemic treatment arm). There was a statistically significant difference in OS in favor of the combined modality arm (hazard ratio [HR] = 0.58, 95% confidence interval [CI] = 0.38 to 0.88, P = .01). Three-, five-, and eight-year OS were 56.9% (95% CI = 43.3% to 68.5%), 43.1% (95% CI = 30.3% to 55.3%), 35.9% (95% CI = 23.8% to 48.2%), respectively, in the combined modality arm and 55.2% (95% CI = 41.6% to 66.9%), 30.3% (95% CI = 19.0% to 42.4%), 8.9% (95% CI = 3.3% to 18.1%), respectively, in the systemic treatment arm. Median OS was 45.6 months (95% CI = 30.3 to 67.8 months) in the combined modality arm vs 40.5 months (95% CI = 27.5 to 47.7 months) in the systemic treatment arm.
Conclusions: This phase II trial is the first randomized study demonstrating that aggressive local treatment can prolong OS in patients with unresectable colorectal liver metastases.
Chemotherapy-induced thrombocytopenia is a common bleeding risk in cancer patients and limits chemotherapy dose and frequency. Recent data from mouse and human platelets revealed that activation of protein kinase A/G (PKA/PKG) not only inhibited thrombin/convulxin-induced platelet activation but also prevented the platelet pro-coagulant state. Here we investigated whether or not PKA/PKG activation could attenuate caspase-dependent apoptosis induced by the anti-cancer drugs ABT-737 (the precursor of navitoclax) and thymoquinone (TQ), thereby potentially limiting chemotherapy-induced thrombocytopenia. This is particularly relevant as activation of cyclic nucleotide signalling in combination chemotherapy is an emerging strategy in cancer treatment. However, PKA/PKG-activation, as monitored by phosphorylation of Vasodilator-stimulated phosphoprotein (VASP), did not block caspase-3-dependent platelet apoptosis induced by the compounds. In contrast, both substances induced PKA activation themselves and PKA activation correlated with platelet inhibition and apoptosis. Surprisingly, ABT-737- and TQ-induced VASP-phosphorylation was independent of cAMP levels and neither cyclases nor phosphatases were affected by the drugs. In contrast, however, ABT-737- and TQ-induced PKA activation was blocked by caspase-3 inhibitors. In conclusion, we show that ABT-737 and TQ activate PKA in a caspase-3-dependent manner, which correlates with platelet inhibition and apoptosis and therefore potentially contributes to the bleeding risk in chemotherapy patients.
First record of a live false killer whale Pseudorca crassidens (Owen, 1846) in Cabo Verdean waters
(2017)
Despite the limited research on cetaceans in Cabo Verde waters, 23 species have been documented (Hazevoet & Wenzel 2000, Hazevoet et al. 2010, Koenen et al. 2013, Berrow et al. 2015). The presence of several species is known only from strandings, such as the false killer whale, which has beached dead twice on Boavista in the 1980s–1990s, and again in 2007 (Hazevoet et al. 2010, Koenen et al. 2013). This is a CITES species, and Data Deficient according to IUCN (Taylor et al. 2008).
Due to its specific features, the German participle has numerous functions and uses in word-formation. As partially deverbalized adjectives, participles take on the syntactic role of an adjective while at the same time retaining the valency of a verb. The paper presents the various steps in an analysis using graded (partial) corpora. Drawing on research into the properties and functions of various participle forms, it explores their specific uses in texts.
In seinem Buch 'Die Verortung der Kultur' analysiert Homi Bhabha das Verhältnis zwischen Literatur, Blasphemie und dem Heiligen. Ihm zufolge ist Blasphemie nicht lediglich eine säkularisierte Fehldarstellung des Heiligen, sondern vielmehr ein Moment, in dem der Inhalt einer kulturellen Tradition im Akt der Übersetzung überwältigt oder verfremdet wird. Bezugnehmend auf Salman Rushdies Roman 'Die Satanischen Verse' stellt Bhabha fest, dass Rushdie einen Raum diskursiver Gegenüberstellung eröffne, der die Autorität des Korans in eine Perspektive des historischen und kulturellen Relativismus hineinstelle.
Zwei Erkenntnisse möchte ich in diesem Ansatz herausheben: Erstens die Kategorie der Übersetzung, die darin besteht, andere artikulatorische Positionen und Möglichkeiten aufzuzeigen. Die zweite Erkenntnis betrifft den historischen und kulturellen Relativismus. Dieser Relativismus ist meines Erachtens für die Heiligkeitsdeutung von entscheidender Bedeutung, da er jegliche festgefahrene und absolute Deutung des Heiligen zunichte macht und die Polyphonie bzw. die Vielfalt der Heiligkeitsauffassungen zulässt. Insbesondere in einem Lebenskontext, der zunehmend von religiöser und kultureller Pluralität gekennzeichnet ist, ist eine solche Vielfalt entscheidend.
Das Buch "Kohelet" des Alten Testaments, auch unter den Titeln "Der Prediger Salomo" oder "Ecclesiastes" überliefert, entstand wahrscheinlich im 3. Jahrhundert vor Christus. Vor allem die Eingangskapitel gehören zu den bekanntesten Texten der sogenannten biblischen Weisheitsbücher. Das kann allein schon die Tradition einiger 'Geflügelter Worte' durch die Jahrhunderte bezeugen wie etwa die folgenden Sätze oder Wendungen: "Es ist alles ganz eitel"; "Nimmersatt"; "Und geschiehet nichts Neues unter der Sonne"; "Ein jegliches hat seine Zeit"; "Sich gütlich tun"; "Viel Büchermachens ist kein Ende".
Spuren eines Einflusses auf das Werk Hofmannsthals scheinen sich etwa im Auftrittsmonolog des "Jedermann" zu finden, wenn er mit seinem stattlichen "Haus", seinem "Hausgesind" oder seinen "Meierhöf voll Vieh" prahlt; denn auch "Kohelet" rühmt sich der von ihm gebauten "Häuser", in denen sein "Gesinde, im Hause geboren" für ihn arbeitet, sowie seiner großen "Habe an Rindern und Schafen".
Diese Übereinstimmungen oder Ähnlichkeiten sind allerdings nur indirekt, weil die direkte Vorlage für Jedermanns Eingangsmonolog eine Dichtung des Hans Sachs ist. Die Textpassage findet sich nicht in Hofmannsthals Hauptquelle, dem "Everyman" aus dem 15. Jahrhundert. So gestaltete sie Hofmannsthal nach seiner zweiten "Jedermann"-Quelle, dem 1549 gedichteten Geistlichen Spiel "Ein comedi von dem reichen sterbenden menschen, der Hecastus genannt".
Borrelia (B.) miyamotoi, an emerging tick-borne relapsing fever spirochete, resists complement-mediated killing. To decipher the molecular principles of immune evasion, we sought to identify determinants contributing to complement resistance. Employing bioinformatics, we identified a gene encoding for a putative Factor H-binding protein, termed CbiA (complement binding and inhibitory protein A). Functional analyses revealed that CbiA interacted with complement regulator Factor H (FH), C3, C3b, C4b, C5, and C9. Upon binding to CbiA, FH retained its cofactor activity for Factor I-mediated inactivation of C3b. The Factor H-binding site within CbiA was mapped to domain 20 whereby the C-terminus of CbiA was involved in FH binding. Additionally, CbiA directly inhibited the activation of the classical pathway and the assembly of the terminal complement complex. Of importance, CbiA displayed inhibitory activity when ectopically produced in serum-sensitive B. garinii G1, rendering this surrogate strain resistant to human serum. In addition, long-term in vitro cultivation lead to an incremental loss of the cbiA gene accompanied by an increase in serum susceptibility. In conclusion, our data revealed a dual strategy of B. miyamotoi to efficiently evade complement via CbiA, which possesses complement binding and inhibitory activities.
Glial cell line-derived neurotrophic factor (GDNF) is a ligand that activates, through co-receptor GDNF family receptor alpha-1 (GFRα1) and receptor tyrosine kinase “RET”, several signaling pathways crucial in the development and sustainment of multiple neuronal populations. We decided to study whether non-mammalian orthologs of these three proteins have conserved their function: can they activate the human counterparts? Using the baculovirus expression system, we expressed and purified Danio rerio RET, and its binding partners GFRα1 and GDNF, and Drosophila melanogaster RET and two isoforms of co-receptor GDNF receptor-like. Our results report high-level insect cell expression of post-translationally modified and dimerized zebrafish RET and its binding partners. We also found that zebrafish GFRα1 and GDNF are comparably active as mammalian cell-produced ones. We also report the first measurements of the affinity of the complex to RET in solution: at least for zebrafish, the Kd for GFRα1-GDNF binding RET is 5.9 μM. Surprisingly, we also found that zebrafish GDNF as well as zebrafish GFRα1 robustly activated human RET signaling and promoted the survival of cultured mouse dopaminergic neurons with comparable efficiency to mammalian GDNF, unlike E. coli-produced human proteins. These results contradict previous studies suggesting that mammalian GFRα1 and GDNF cannot bind and activate non-mammalian RET and vice versa.
The 33S(n,α)30Si cross section measurement, using 10B(n,α) as reference, at the n_TOF Experimental Area 2 (EAR2) facility at CERN is presented. Data from 0.01 eV to 100 keV are provided and, for the first time, the cross section is measured in the range from 0.01 eV to 10 keV. These data may be used for a future evaluation of the cross section because present evaluations exhibit large discrepancies. The 33S(n,α)30Si reaction is of interest in medical physics because of its possible use as a cooperative target to boron in Neutron Capture Therapy (NCT).
In seinem Buch 'Die Verortung der Kultur' analysiert Homi Bhabha das Verhältnis zwischen Literatur, Blasphemie und dem Heiligen. Ihm zufolge ist Blasphemie nicht lediglich eine säkularisierte Fehldarstellung des Heiligen, sondern vielmehr ein Moment, in dem der Inhalt einer kulturellen Tradition im Akt der Übersetzung überwältigt oder verfremdet wird. Bezugnehmend auf Salman Rushdies Roman 'Die Satanischen Verse' stellt Bhabha fest, dass Rushdie einen Raum diskursiver Gegenüberstellung eröffne, der die Autorität des Korans in eine Perspektive des historischen und kulturellen Relativismus hineinstelle.
Zwei Erkenntnisse möchte ich in diesem Ansatz herausheben: Erstens die Kategorie der Übersetzung, die darin besteht, andere artikulatorische Positionen und Möglichkeiten aufzuzeigen. Die zweite Erkenntnis betrifft den historischen und kulturellen Relativismus. Dieser Relativismus ist meines Erachtens für die Heiligkeitsdeutung von entscheidender Bedeutung, da er jegliche festgefahrene und absolute Deutung des Heiligen zunichte macht und die Polyphonie bzw. die Vielfalt der Heiligkeitsauffassungen zulässt. Insbesondere in einem Lebenskontext, der zunehmend von religiöser und kultureller Pluralität gekennzeichnet ist, ist eine solche Vielfalt entscheidend.
In diesem Beitrag wurden deutsche Entlehnungen in der albanischen Mundart in Kosova untersucht, welche in verschiedenen semantischen Bereichen verwendet werden. Schriftliche Quellen zu diesen Germanismen fehlen völlig, daher wurden sie durch mündliche Befragung von Informanten inventarisiert. Den Schwerpunkt dieser Untersuchung bilden der Bekanntheitsgrad und die Akzeptanz dieser Lehnwörter. Die Befragung hat ergeben, dass die Lehnwörter in den hier untersuchten semantischen Bereichen durchschnittlich von über 70% der Befragten erkannt wurden. Im Allgemeinen konnten keine großen Unterschiede im Erkennungsgrad bei männlichen und weiblichen Befragten festgestellt werden, wohingegen bei der Variable Alter eine etwas größere Diskrepanz beobachtet wurde, was das Erkennen oder Nichterkennen der deutschen Entlehnungen anging.
Este artigo visa discutir os modelos de síntese pressupostos pela dialética negativa de Adorno através de aproximações de temáticas maiores da filosofia de Karl Marx. Isto nos permitirá qualificar melhor a natureza materialista da dialética negativa adorniana, abordando inclusive o impacto político de certas elaborações conceituais.
We present a novel equation of state which is based on the virial expansion for the multicomponent mixtures with hard core repulsion. The suggested equation of state explicitly contains the surface tension which is induced by particle interaction. At high densities such a surface tension vanishes and in this way it switches the excluded volume treatment of hard core repulsion to its eigen volume treatment. The great advantage of the developed model is that the number of equations to be solved is two and it does not depend on the number of independent hard-core radii. Using the suggested equation of state we obtained a high quality fit of the hadron multiplicities measured at AGS, SPS, RHIC and ALICE energies and studied the properties of the nuclear matter phase diagram. It is shown the developed equation of state is softer than the gas of hard spheres and remains causal up to the several normal nuclear densities. Therefore, it could be applied to the neutron star interior modeling.
Short range particle repulsion is rather important property of the hadronic and nuclear matter equations of state. We present a novel equation of state which is based on the virial expansion for the multicomponent mixtures with hard-core repulsion. In addition to the hard-core repulsion taken into account by the proper volumes of particles, this equation of state explicitly contains the surface tension which is induced by another part of the hard-core repulsion between particles. At high densities the induced surface tension vanishes and the excluded volume treatment of hard-core repulsion is switched to its proper volume treatment. Possible applications of this equation of state to a description of hadronic multiplicities measured in A+A collisions, to an investigation of the nuclear matter phase diagram properties and to the neutron star interior modeling are discussed.
The formation of acquired drug resistance is a major reason for the failure of anti-cancer therapies after initial response. Here, we introduce a novel model of acquired oxaliplatin resistance, a sub-line of the non-MYCN-amplified neuroblastoma cell line SK-N-AS that was adapted to growth in the presence of 4000 ng/mL oxaliplatin (SK-N-ASrOXALI4000). SK-N-ASrOXALI4000 cells displayed enhanced chromosomal aberrations compared to SK-N-AS, as indicated by 24-chromosome fluorescence in situ hybridisation. Moreover, SK-N-ASrOXALI4000 cells were resistant not only to oxaliplatin but also to the two other commonly used anti-cancer platinum agents cisplatin and carboplatin. SK-N-ASrOXALI4000 cells exhibited a stable resistance phenotype that was not affected by culturing the cells for 10 weeks in the absence of oxaliplatin. Interestingly, SK-N-ASrOXALI4000 cells showed no cross resistance to gemcitabine and increased sensitivity to doxorubicin and UVC radiation, alternative treatments that like platinum drugs target DNA integrity. Notably, UVC-induced DNA damage is thought to be predominantly repaired by nucleotide excision repair and nucleotide excision repair has been described as the main oxaliplatin-induced DNA damage repair system. SK-N-ASrOXALI4000 cells were also more sensitive to lysis by influenza A virus, a candidate for oncolytic therapy, than SK-N-AS cells. In conclusion, we introduce a novel oxaliplatin resistance model. The oxaliplatin resistance mechanisms in SK-N-ASrOXALI4000 cells appear to be complex and not to directly depend on enhanced DNA repair capacity. Models of oxaliplatin resistance are of particular relevance since research on platinum drugs has so far predominantly focused on cisplatin and carboplatin.
Autophagy is a membrane-trafficking process that directs degradation of cytoplasmic material in lysosomes. The process promotes cellular fidelity, and while the core machinery of autophagy is known, the mechanisms that promote and sustain autophagy are less well defined. Here we report that the epigenetic reader BRD4 and the methyltransferase G9a repress a TFEB/TFE3/MITF-independent transcriptional program that promotes autophagy and lysosome biogenesis. We show that BRD4 knockdown induces autophagy in vitro and in vivo in response to some, but not all, situations. In the case of starvation, a signaling cascade involving AMPK and histone deacetylase SIRT1 displaces chromatin-bound BRD4, instigating autophagy gene activation and cell survival. Importantly, this program is directed independently and also reciprocally to the growth-promoting properties of BRD4 and is potently repressed by BRD4-NUT, a driver of NUT midline carcinoma. These findings therefore identify a distinct and selective mechanism of autophagy regulation.
HADES experiment at GSI is the only high precision experiment probing nuclear matter in the beam energy range of a few AGeV. Pion, proton and ion beams are used to study rare dielectron and strangeness probes to diagnose properties of strongly interacting matter in this energy regime. Selected results from p + A and A + A collisions are presented and discussed.
Schiller and Goethe have very different conceptions of tragedy. In his play Don Carlos, Schiller, especially in the character of Philip II, shows us the conflict between blood and positive law. In Goethe´s novel Elective Affinities, the individual will is ignorant of fate and helpless against it. So to speak, Schiller applies the "Antigone´s Model" and Goethe applies the "Oedipus Model". In his dramatic vision of the conflict, Schiller is inspired by Shakespeare´s plays. However, Goethe´s point of view is based on his reflections on Natural Philosophy.
Land surface and hydrologic models (LSMs/HMs) are used at diverse spatial resolutions ranging from catchment-scale (1–10 km) to global-scale (over 50 km) applications. Applying the same model structure at different spatial scales requires that the model estimates similar fluxes independent of the chosen resolution, i.e., fulfills a flux-matching condition across scales. An analysis of state-of-the-art LSMs and HMs reveals that most do not have consistent hydrologic parameter fields. Multiple experiments with the mHM, Noah-MP, PCR-GLOBWB, and WaterGAP models demonstrate the pitfalls of deficient parameterization practices currently used in most operational models, which are insufficient to satisfy the flux-matching condition. These examples demonstrate that J. Dooge's 1982 statement on the unsolved problem of parameterization in these models remains true. Based on a review of existing parameter regionalization techniques, we postulate that the multiscale parameter regionalization (MPR) technique offers a practical and robust method that provides consistent (seamless) parameter and flux fields across scales. Herein, we develop a general model protocol to describe how MPR can be applied to a particular model and present an example application using the PCR-GLOBWB model. Finally, we discuss potential advantages and limitations of MPR in obtaining the seamless prediction of hydrological fluxes and states across spatial scales.
Land surface and hydrologic models (LSM/HM) are used at diverse spatial resolutions ranging from 1-10 km in catchment-scale applications to over 50 km in global-scale applications. Application of the same model structure at different spatial scales requires that the model estimates similar fluxes independent of the model resolution and fulfills a flux-matching condition across scales. An analysis of state-of-the-art LSMs and HMs reveals that most do not have consistent and realistic parameter fields for land surface geophysical properties. Multiple experiments with the mHM, Noah-MP, PCR-GLOBWB and WaterGAP models are conducted to demonstrate the pitfalls of poor parameterization practices currently used in most operational models, which are insufficient to satisfy the flux-matching condition. These examples demonstrate that J. Dooge’s 1982 statement on the unsolved problem of parameterization in these models remains true. We provide a short review of existing parameter regionalization techniques and discuss a method for obtaining seamless hydrological predictions of water fluxes and states across multiple spatial resolutions. The multiscale parameter regionalization (MPR) technique is a practical and robust method that provides consistent (seamless) parameter and flux fields across scales. A general model protocol is presented to describe how MPR can be applied to a specific model, with an example of this application using the PCR-GLOBWB model. Applying MPR to PCR-GLOBWB substantially improves the flux-matching condition. Estimation of evapotranspiration without MPR at 5 arcmin and 30 arcmin spatial resolutions for the Rhine river basin results in a difference of approximately 29%. Applying MPR reduce this difference to 9%. For total soil water, the differences without and with MPR are 25% and 7%, respectively.
A booming middle class, new attractive study destinations and a resulting shift in student mobility trends have recently established a new dynamic in international higher education. To stay competitive, countries apply marketing strategies to promote and "sell" their higher education to international students-cum-customers. With the growing use of the Internet to research study destinations, the role of online channels in higher education promotion is becoming increasingly important. The current study investigates the case of Malaysian higher education branding in cyberspace. By applying content analysis to the two major higher education online platforms, this study identifies the core brand values of Malaysian higher education and evaluates their coherence. The research findings demonstrate that both platforms combine nation and higher education branding efforts to create a harmonised image of the national higher education system. Additionally, several suggestions are made concerning the optimisation of the architecture and information presentation of the websites to enhance their attractiveness for users. Finally, the necessity of further investigation into higher education branding for the successful implementation of internationalisation policies in Malaysia is emphasised.
Taxonomically dissimilar epiphyte species can have comparable morphological and physiological traits in similar environmental conditions. However, the degree of trait similarity has not been examined in a comparison of bryophytic and vascular epiphytes across elevational and tree gradients. We assess whether epiphyte species that occupy comparable realised niche spaces within host tree and landscape scale gradients have similarities in taxonomy, morphology or physiology. Vascular and moss epiphytes were surveyed within four height zones at five elevations (300-1100 m asl) in the sub-tropical rainforest of Australia. Epiphyte species distributions were agglomeratively classified using Ward’s method. Chi square tests were used to test for differences in the incidences of taxonomic groups, life forms, leaf thickness, photosynthetic pathways and other drought resistant morphologies between these distributional groups. These traits were also tested for correlation with light and humidity. Six groups were identified based on distribution. Vascular epiphytes with CAM, thickened leaves and other drought-mitigating morphologies were common in the groups that occupied the most xeric situations. All drought resistant traits were associated with high light and low humidity. Vascular species with few to no drought-mitigating characteristics were common in groups that occupied moister situations. Moss morphology was less congruent with environmental conditions than vascular plant morphology, suggesting that moss life forms are responding to a different scale of environmental variation.
O ensaio traz como base a crítica ao capitalismo, no que se refere aos efeitos negativos que ele impõe aos indivíduos, a partir dos estudos da primeira geração da Escola de Frankfurt. Analisar-se-á a história das ideias a partir de Walter Benjamin, Herbert Marcuse, Theodor Adorno e Max Horkheimer. Benjamin afirma que vive-se a perda da aura das obras de arte, já que a sua comercialização faz com que se perca a essência daquelas obras. Ademais, a imposição da novidade às obras e aos produtos consumidos representa uma ferramenta de manipulação do capitalismo, culminando na pobreza da experiência humana. Marcuse afirma que a sociedade vive o princípio do desempenho, que provoca modos de vida uniformizados, baseados numa concepção de trabalho e diversão homogêneos. Adorno propôs que o tempo livre provocava uma sensação de liberdade nos indivíduos, mas, na realidade, tratava-se do exercício de uma não liberdade, já que as formas de diversão seguiam à risca os padrões exigidos pelo capital. A partir do método adotado pela própria Teoria Crítica, afirma-se que a presente discussão teórica só se torna efetiva quando aplicada à prática, à sociedade atual.
The population size and distribution of Phaethon aethereus on Raso Islet was studied from August to December 2016. In total, 42 biometric measures were collected from 38 adults and four juveniles. No recapture was identified although some individuals were ringed in 2014. The means of biometrics variables obtained for the different body segments and eggs were within the ranges of P. aethereus mesonauta from tropical North Atlantic. The two largest agglomerations of P. aethereus identified on Raso were overlapping colonies of brown boobies Sula leucogaster which allowed the maximum direct count of only 90 individuals. The inaccessibility of some breeding areas conditioned the identification and monitoring of just 117 nests. Thus, we estimate the population by the number of nests in more than 100 pairs. However, without an annual census, it is difficult to estimate the population size of this species. So, annual studies are recommended to better understand the population dynamics of P. aethereus on Raso.
Objective: The glucose stimulation of insulin secretion (GSIS) by pancreatic β-cells critically depends on increased production of metabolic coupling factors, including NADPH. Nicotinamide nucleotide transhydrogenase (NNT) typically produces NADPH at the expense of NADH and ΔpH in energized mitochondria. Its spontaneous inactivation in C57BL/6J mice was previously shown to alter ATP production, Ca2+ influx, and GSIS, thereby leading to glucose intolerance. Here, we tested the role of NNT in the glucose regulation of mitochondrial NADPH and glutathione redox state and reinvestigated its role in GSIS coupling events in mouse pancreatic islets.
Methods: Islets were isolated from female C57BL/6J mice (J-islets), which lack functional NNT, and genetically close C57BL/6N mice (N-islets). Wild-type mouse NNT was expressed in J-islets by adenoviral infection. Mitochondrial and cytosolic glutathione oxidation was measured with glutaredoxin 1-fused roGFP2 probes targeted or not to the mitochondrial matrix. NADPH and NADH redox state was measured biochemically. Insulin secretion and upstream coupling events were measured under dynamic or static conditions by standard procedures.
Results: NNT is largely responsible for the acute glucose-induced rise in islet NADPH/NADP+ ratio and decrease in mitochondrial glutathione oxidation, with a small impact on cytosolic glutathione. However, contrary to current views on NNT in β-cells, these effects resulted from a glucose-dependent reduction in NADPH consumption by NNT reverse mode of operation, rather than from a stimulation of its forward mode of operation. Accordingly, the lack of NNT in J-islets decreased their sensitivity to exogenous H2O2 at non-stimulating glucose. Surprisingly, the lack of NNT did not alter the glucose-stimulation of Ca2+ influx and upstream mitochondrial events, but it markedly reduced both phases of GSIS by altering Ca2+-induced exocytosis and its metabolic amplification.
Conclusion: These results drastically modify current views on NNT operation and mitochondrial function in pancreatic β-cells.
HADES is a fixed target experiment using SIS18 heavy-ion beams. It investigates the microscopic properties of matter formed in heavy-ion, proton and pion - induced reactions in the 1-3.5 GeV/u energy regime. In 2014 HADES used a secondary pion beam produced by interaction between high-intensity nitrogen primary beam and a beryllium target. In these conditions beam losses, generated by slow extraction and beam transport to the experimental area, led to activation of the beam line elements and triggered radiation alarms. The primary beam intensity had to be reduced and the beam optics modified in order to keep radiation levels within the allowed limits. Similar beam conditions are requested by HADES experiment for upcoming run in 2018 and in the following years. Therefore, a number of measures have been proposed to improve beam transmission and quality. These measures are: additional shielding, additional beam instrumentation, modification of beam optics and increase of vacuum chambers' apertures in critical locations. The optics study and preliminary results of FLUKA simulations for optimization of location of loss detectors are presented.
Excessive neutrophil activation accompanied by delayed apoptotic cell death in inflammatory conditions causes progressive damage of cells and tissues, leading to life-threatening multiple organ dysfunction syndrome. Previous work suggested that circulating serum factors during inflammation are critically involved in the suppression of neutrophil cell death although the identity of these antiapoptotic mediators remained elusive. In this study, we identified the acute phase protein α-1 Antitrypsin (AAT) as a potent suppressor of staurosporine (STS)-induced apoptosis in human neutrophils through a mechanism implicating caspases-independent pathways. We show here that serum levels of AAT, potentially in part released by stimulated neutrophils, are markedly elevated in major trauma patients suffering from systemic inflammatory response syndrome (SIRS). Notably, AAT depletion from serum increased sensitivity of human neutrophils for STS-induced cell death. In fact, AAT was demonstrated to confer intrinsic apoptosis resistance by preventing PKC/Akt inactivation and subsequent proteasomal degradation of antiapoptotic Mcl-1 protein in response to STS treatment. Neither MAP kinase ERK1/2 nor caspases were found to be involved in AAT-triggered antiapoptotic pathways in neutrophils. In summary, these results establish a novel pivotal role of circulating AAT in mediating survival by antagonizing the proapoptotic action of the PKC inhibitor STS and should be considered for AAT augmentation therapies in future.
The efficacy of cisplatin-based chemotherapy in cancer is limited by the occurrence of innate and acquired drug resistance. In order to better understand the mechanisms underlying acquired cisplatin resistance, we have compared the adenocarcinoma-derived non-small cell lung cancer (NSCLC) cell line A549 and its cisplatin-resistant sub-line A549rCDDP2000 with regard to cisplatin resistance mechanisms including cellular platinum accumulation, DNA-adduct formation, cell cycle alterations, apoptosis induction and activation of key players of DNA damage response. In A549rCDDP2000 cells, a cisplatin-induced G2/M cell cycle arrest was lacking and apoptosis was reduced compared to A549 cells, although equitoxic cisplatin concentrations resulted in comparable platinum-DNA adduct levels. These differences were accompanied by changes in the expression of proteins involved in DNA damage response. In A549 cells, cisplatin exposure led to a significantly higher expression of genes coding for proteins mediating G2/M arrest and apoptosis (mouse double minute 2 homolog (MDM2), xeroderma pigmentosum complementation group C (XPC), stress inducible protein (SIP) and p21) compared to resistant cells. This was underlined by significantly higher protein levels of phosphorylated Ataxia telangiectasia mutated (pAtm) and p53 in A549 cells compared to their respective untreated control. The results were compiled in a preliminary model of resistance-associated signaling alterations. In conclusion, these findings suggest that acquired resistance of NSCLC cells against cisplatin is the consequence of altered signaling leading to reduced G2/M cell cycle arrest and apoptosis.
Recruitment of inflammatory cells is a major feature of alcoholic liver injury however; the signals and cellular sources regulating this are not well defined. C-C chemokine receptor type 2 (CCR2) is expressed by active hepatic stellate cells (HSC) and is a key monocyte recruitment signal. Activated HSC are also important sources of hydrogen peroxide resulting from the activation of NADPH oxidase 4 (NOX4). As the role of this NOX in early alcoholic liver injury has not been addressed, we studied NOX4-mediated regulation of CCR2/CCL2 mRNA stability. NOX4 mRNA was significantly induced in patients with alcoholic liver injury, and was co-localized with αSMA-expressing activated HSC. We generated HSC-specific NOX4 KO mice and these were pair-fed on alcohol diet. Lipid peroxidation have not changed significantly however, the expression of CCR2, CCL2, Ly6C, TNFα, and IL-6 was significantly reduced in NOX4HSCKO compared to fl/fl mice. NOX4 promoter was induced in HSC by acetaldehyde treatment, and NOX4 has significantly increased mRNA half-life of CCR2 and CCL2 in conjunction with Ser221 phosphorylation and cytoplasmic shuttling of HuR. In conclusion, NOX4 is induced in early alcoholic liver injury and regulates CCR2/CCL2 mRNA stability thereby promoting recruitment of inflammatory cells and production of proinflammatory cytokines.
Erwin Wittstock (1899-1962), the writer of German expression from Romania, has created a monumental body of works (short stories and novels), which stem from German history and culture from Transylvania. The characters he created are projections of his own life. His novel Januar ’45 oder Die höhere Pflicht, reviewed in the present article from an intercultural point of view, is dedicated to the problem of deportation, a topic which was taboo in the communist regime. His work on the topic is shaped into a novel in Balzacian style, the author writing from the perspective of an eye witness. The problematic invites the description of power, of terror and of repression in totalitarian states. As member of the German community in Romania he depicts the Transylvanian multiethnic and multicultural society in his fiction. The elements of interculturality in his novel can be summarized as: social interethnic relations, imagology, respectively the outlining of the image of otherness, also on a linguistic level.
We derive three exact sum rules for the spectral function of the electromagnetic current with zero spatial momentum at finite temperature. Possible applications of the three sum rules to lattice computations of the spectral function and transport coefficients are also discussed: We propose an ansatz for the spectral function that can be applied to all three sum rules and fit it to available lattice data of the Euclidean vector correlator above the critical temperature. As a result, we obtain estimates for both the electrical conductivity σ and the second order transport coefficient τJ.
Was Du heute kannst besorgen, das verschiebe nicht auf morgen: Dieser sprichwörtliche Rat kommt nicht von ungefähr. Viele von uns schieben oft wochenlang eine Aufgabe vor sich her – häufig mit schlechtem Gewissen. Doch woher kommt das ewige Aufschieben eigentlich? Wer ist davon betroffen? Und was kann man dagegen tun?
Der Mensch besteht aus vielen Körperteilen, und doch ist es fast ausschließlich das Gesicht, an dem wir ein Individuum erkennen. Aber erkennen wir es wirklich? In Zeiten des Selfie-Kults und der biometrischen Verfahren ist diese Frage aktueller denn je. Wir leben in einer »fazialen« Gesellschaft: Das Gesicht ist Medium für alle erdenklichen Arten, sich mitzuteilen.
Verschlafen? Ausgeschlafen!
(2017)
The bilingual phraseography with German contains significant shortcomings regarding both the conceptional orientation of the dictionary and the structure of the dictionary articles. The present paper reflects upon the relevance of certain criteria that are decisive for the quality of a dictionary and aims at showing to what extent the description of the selected phraseologisms is adequate with regard to potential users and the specifics of phraseological phenomena.
Based on the specific use of fixed expressions in everyday communication or in written messages, the paper presents modifications of reiterated discourse (suppresion, addition, substitution, permutation) that are illustrated by adapted common phrases and innovations of text types with formalized language.
Cette étude analyse les stratégies locales de dénomination des espèces végétales par les Mossé des régions du nord, du centre nord, du centre et du Plateau Central du Burkina Faso et leurs perceptions des plantes. A travers des interviews semi directes auprès de 1437 personnes âgées d’au moins 60 ans et des jeunes de moins de 40 ans des différentes localités, l’étude a pu montrer les critères de dénomination, les conceptions que les populations ont des espèces végétales ainsi que l‘impact de ces connaissances dans la conservation de la phytodiversité. 72 espèces au total ont été décrites. Elles sont réparties en 51 genres et 29 familles. Les familles dominantes sont les Commelinaceae et les Fabaceae-Mimosoideae. Dans la taxonomie locale faite sur les plantes en milieu rural Mossé, 16 critères sont utilisés. Les critères les plus cités par la population sont l’usage fait de la plante (94 %), le mysticisme lié à l’espèce (86 %), l’écologie ou le milieu de vie de l’espèce (83 %), la dualité mâle/femelle (83 %), la couleur des organes ou parties de la plante (81 %), l’origine de la plante (80 %), la morphologie foliaire (76 %), la présence d’organes saillants sur la plante (75 %) et le mode de dissémination des fruits ou des graines (74 %). Les noms botaniques attribués aux plantes varient d’une région à une autre. Les populations ont des perceptions vis-à-vis de nombreuses espèces. Ainsi, les espèces comme Stereospermum kunthianum, Calotropis procera, Ozoroa insignis, Faidherbia albida, Maytenus senegalensis et Biophytum umbraculum sont frappées de mysticisme. Elles sont toutes craintes par les populations et sont dans certaines localités à l’abri d’exploitations multiformes humaines. Cela contribue à une meilleure conservation de la biodiversité.
Com o advento da modernidade a filosofia passou a exigir que a religião prestasse contas à razão. A filosofia da religião de Kant é um exemplo desse tipo de iniciativa. Kant propôs julgar a religião no tribunal da razão. Mais de 200 anos depois, Habermas buscou renovar o projeto kantiano. Nosso trabalho visa esclarecer o modo como cada autor realiza o julgamento da religião no tribunal da razão. Além disso, discutiremos a relevância desse tipo de abordagem proposta por ambos os filósofos.
In mammals, acoustic communication plays an important role during social behaviors. Despite their ethological relevance, the mechanisms by which the auditory cortex represents different communication call properties remain elusive. Recent studies have pointed out that communication-sound encoding could be based on discharge patterns of neuronal populations. Following this idea, we investigated whether the activity of local neuronal networks, such as those occurring within individual cortical columns, is sufficient for distinguishing between sounds that differed in their spectro-temporal properties. To accomplish this aim, we analyzed simple pure-tone and complex communication call elicited multi-unit activity (MUA) as well as local field potentials (LFP), and current source density (CSD) waveforms at the single-layer and columnar level from the primary auditory cortex of anesthetized Mongolian gerbils. Multi-dimensional scaling analysis was used to evaluate the degree of “call-specificity” in the evoked activity. The results showed that whole laminar profiles segregated 1.8-2.6 times better across calls than single-layer activity. Also, laminar LFP and CSD profiles segregated better than MUA profiles. Significant differences between CSD profiles evoked by different sounds were more pronounced at mid and late latencies in the granular and infragranular layers and these differences were based on the absence and/or presence of current sinks and on sink timing. The stimulus-specific activity patterns observed within cortical columns suggests that the joint activity of local cortical populations (as local as single columns) could indeed be important for encoding sounds that differ in their acoustic attributes.
Human immunodeficiency virus type 1 (HIV-1) infection of dividing and nondividing cells involves regulatory interactions with the nuclear pore complex (NPC), followed by translocation to the nucleus and preferential integration into genomic areas in proximity to the inner nuclear membrane (INM). To identify host proteins that may contribute to these processes, we performed an overexpression screen of known membrane-associated NE proteins. We found that the integral transmembrane proteins SUN1/UNC84A and SUN2/UNC84B are potent or modest inhibitors of HIV-1 infection, respectively, and that suppression corresponds to defects in the accumulation of viral cDNA in the nucleus. While laboratory strains (HIV-1NL4.3 and HIV-1IIIB) are sensitive to SUN1-mediated inhibition, the transmitted founder viruses RHPA and ZM247 are largely resistant. Using chimeric viruses, we identified the HIV-1 capsid (CA) protein as a major determinant of sensitivity to SUN1, and in vitro-assembled capsid-nucleocapsid (CANC) nanotubes captured SUN1 and SUN2 from cell lysates. Finally, we generated SUN1−/− and SUN2−/− cells by using CRISPR/Cas9 and found that the loss of SUN1 had no effect on HIV-1 infectivity, whereas the loss of SUN2 had a modest suppressive effect. Taken together, these observations suggest that SUN1 and SUN2 may function redundantly to modulate postentry, nuclear-associated steps of HIV-1 infection.
IMPORTANCE HIV-1 causes more than 1 million deaths per year. The life cycle of HIV-1 has been studied extensively, yet important steps that occur between viral capsid release into the cytoplasm and the expression of viral genes remain elusive. We propose here that the INM components SUN1 and SUN2, two members of the linker of nucleoskeleton and cytoskeleton (LINC) complex, may interact with incoming HIV-1 replication complexes and affect key steps of infection. While overexpression of these proteins reduces HIV-1 infection, disruption of the individual SUN2 and SUN1 genes leads to a mild reduction or no effect on infectivity, respectively. We speculate that SUN1/SUN2 may function redundantly in early HIV-1 infection steps and therefore influence HIV-1 replication and pathogenesis.
Morphological malformations induced by tributyltin (TBT) exposure during embryonic development have already been characterized in various taxonomic groups, but, nonetheless, the molecular processes underlying these changes remain obscure. The present study provides the first genome-wide screening for differentially expressed genes that are linked to morphological alterations of gonadal tissue from chicken embryos after exposure to TBT. We applied a single injection of TBT (between 0.5 and 30 pg as Sn/g egg) into incubated fertile eggs to simulate maternal transfer of the endocrine disruptive compound. Methyltestosterone (MT) served as a positive control (30 pg/g egg). After 19 days of incubation, structural features of the gonads as well as genome-wide gene expression profiles were assessed simultaneously. TBT induced significant morphological and histological malformations of gonadal tissue from female embryos that show a virilization of the ovaries. This phenotypical virilization was mirrored by altered expression profiles of sex-dependent genes. Among these are several transcription and growth factors (e.g. FGF12, CTCF, NFIB), whose altered expression might serve as a set of markers for early identification of endocrine active chemicals that affect embryonic development by transcriptome profiling without the need of elaborate histological analyses.
Characterization of a novel KCNJ2 sequence variant detected in Andersen-Tawil syndrome patients
(2017)
Background: Mutations in the KCNJ2 gene encoding the ion channel Kir2.1 have been linked to the Andersen-Tawil syndrome (ATS). Molecular genetic screening performed in a family exhibiting clinical ATS phenotypes unmasked a novel sequence variant (c.434A > G, p.Y145C) in this gene. The aim of this study was to investigate the effect of this variant on Kir2.1 ion channel functionality.
Methods: Mutant as well as wild type GFP tagged Kir2.1 channels were expressed in HEK293 cells. In order to examine the effect of the new variant, electrophysiological measurements were performed using patch clamp technique. Cellular localization of the mutant in comparison to the wild type ion channel was analyzed by confocal laser scanning microscopy.
Results: The currents of cells expressing only mutant channels or a mixture of wild type and mutant were significantly reduced compared to those expressing wild type (WT) channels (p < 0.01). Whereas WT expressing cells exhibited at −120 mV an averaged current of −4.5 ± 1.9 nA, the mutant generates only a current of −0.17 ± 0.07 nA. A co-expression of mutant and WT channel generates only a partial rescue of the WT current. Confocal laser scanning microscopy indicated that the novel variant is not interfering with synthesis and/or protein trafficking.
Conclusions: The detected sequence variant causes loss-of-function of the Kir2.1 channel and explains the clinical phenotypes observed in Andersen-Tawil syndrome patients.
Molluscs are the second most species-rich phylum in the animal kingdom, yet only 11 genomes of this group have been published so far. Here, we present the draft genome sequence of the pulmonate freshwater snail Radix auricularia. Six whole genome shotgun libraries with different layouts were sequenced. The resulting assembly comprises 4,823 scaffolds with a cumulative length of 910 Mb and an overall read coverage of 72×. The assembly contains 94.6% of a metazoan core gene collection, indicating an almost complete coverage of the coding fraction. The discrepancy of ∼690 Mb compared with the estimated genome size of R. auricularia (1.6 Gb) results from a high repeat content of 70% mainly comprising DNA transposons. The annotation of 17,338 protein coding genes was supported by the use of publicly available transcriptome data. This draft will serve as starting point for further genomic and population genetic research in this scientifically important phylum.
The effect-response framework states that plant functional traits link the abiotic environment to ecosystem functioning. One ecosystem property is the body size of the animals living in the system, which is assumed to depend on temperature or resource availability, among others. For primary consumers, resource availability may directly be related to plant traits, while for secondary consumers the relationship is indirect. We used plant traits to describe resource availability along an elevational gradient on Mount Kilimanjaro, Tanzania. Using structural equation models, we determined the response of plant traits to changes in precipitation, temperature and disturbance with and assessed whether abiotic conditions or community-weighted means of plant traits are stronger predictors of the mean size of bees, moths, frugivorous birds, and insectivorous birds. Traits indicating tissue density and nutrient content strongly responded to variations in precipitation, temperature and disturbance. They had direct effects on pollination and fruit traits. However, the average body sizes of the animal groups considered could only be explained by temperature and habitat structure, not by plant traits. Our results demonstrate a strong link between traits and the abiotic environment, but suggest that temperature is the most relevant predictor of mean animal body size. Community-weighted means of plant traits and body sizes appear unsuitable to capture the complexity of plant-animal interactions.
Wer spricht wie über wen? Diese Frage wird im Folgenden an die dokumentarischen Kinderhörspiele Kinder auf der Flucht, damals und heute (2015) und Jeden Tag ein bisschen ankommen. Flüchtlingskinder in einer Dortmunder Willkommensklasse (2015) als Erzählformen über Migration und Flucht, die repräsentative und identitätsstiftende Angebote machen, gestellt. An diesen Aspekten setzen kritische Fragen nach der Möglichkeit der Artikulation von Kindern als GestalterInnen postmigrantischen Zusammenlebens an. Dabei wird speziell in den Blick genommen, ob und wie Kinder als bevormundete Personen, die darüber hinaus durch den Status geflüchtet markiert sind, einer doppelten Herausforderung des Sprechens und Gehörtwerdens begegnen. Der Fokus der Untersuchung richtet sich darauf, wie in den Radiogeschichten das Verhältnis von Originalton-Material und personifizierter Erzählinstanz gestaltet ist, welche definierenden Konzepte und Begriffe zum Einsatz kommen und wo sich subversive Erzählmomente finden lassen. ...
Feeding type and development drive the ingestion of microplastics by freshwater invertebrates
(2017)
Microscopic plastic items (microplastics) are ubiquitously present in aquatic ecosystems. With decreasing size their availability and potential to accumulate throughout food webs increase. However, little is known on the uptake of microplastics by freshwater invertebrates. To address this, we exposed species with different feeding strategies to 1, 10 and 90 µm fluorescent polystyrene spheres (3–3 000 particles mL−1). Additionally, we investigated how developmental stages and a co-exposure to natural particles (e.g., food) modulate microplastic ingestion. All species ingested microplastics in a concentration-dependent manner with Daphnia magna consuming up to 6 180 particles h−1, followed by Chironomus riparius (226 particles h−1), Physella acuta (118 particles h−1), Gammarus pulex (10 particles h−1) and Lumbriculus variegatus (8 particles h−1). D. magna did not ingest 90 µm microplastics whereas the other species preferred larger microplastics over 1 µm in size. In C. riparius and D. magna, size preference depended on the life stage with larger specimens ingesting more and larger microplastics. The presence of natural particles generally reduced the microplastics uptake. Our results demonstrate that freshwater invertebrates have the capacity to ingest microplastics. However, the quantity of uptake depends on their feeding type and morphology as well as on the availability of microplastics.
Von Natur aus, so Döblin, kannte das Epische in seiner "unbegrenzten Form" kein bestimmtes Ende. Realität, Traum und Phantasie waren noch nicht voneinander geschieden; berichtet wurden "Elementarsituationen des menschlichen Daseins" in "immer neuen Abwandlungen", in der "Serienarbeit" der mündlichen und kollektiven Erzählungen und Nacherzählungen, im Grunde der "Wahrheit" ohne Begründung. Auf Einladung des Germanistikprofessors Julius Petersen hielt Döblin am 10. Dezember 1928 seinen Vortrag "Der Bau des epischen Werks" im Auditorium Maximum der Berliner Friedrich-Wilhelms-Universität. Darin erstellt er ein Programm zur Erneuerung des Romans unter den Bedingungen der modernen Kollektiverfahrungen von Masse, Technik und medialer Öffentlichkeit, in Verbindung mit den Wissensbeständen von Medizin, Psychiatrie und Soziologie und deren "Resonanz", wie er in seiner ganz persönlichen Universalschrift 'Unser Dasein' von 1933 schrieb, seiner letzten in Deutschland vor dem Exil erschienenen Publikation. Die Literatur hätte die Aufgabe, die neu entstandene Wirklichkeit zu "durchstoßen", das Menschenmögliche, auch die destruktiven Energien zur Sprache zu bringen: im Produktionsprozess eines als "dynamisches Netzwerk" zu begreifenden und plastisch zu gestaltenden Weltganzen, der Dinge und Vorgänge mit den in ihnen wirkenden Kräften. Die Vitalisierung und Elementarisierung der Sprache sollte den Ursprung des Epischen wiedergewinnen und die vorherrschende Repräsentationslogik der medialen Vermittlung außer Kraft setzen: "Das Buch ist der Tod der wirklichen Sprache."
Biogenesis of mitochondrial cytochrome c oxidase (COX) is a complex process involving the coordinate expression and assembly of numerous subunits (SU) of dual genetic origin. Moreover, several auxiliary factors are required to recruit and insert the redox-active metal compounds, which in most cases are buried in their protein scaffold deep inside the membrane. Here we used a combination of gel electrophoresis and pull-down assay techniques in conjunction with immunostaining as well as complexome profiling to identify and analyze the composition of assembly intermediates in solubilized membranes of the bacterium Paracoccus denitrificans. Our results show that the central SUI passes through at least three intermediate complexes with distinct subunit and cofactor composition before formation of the holoenzyme and its subsequent integration into supercomplexes. We propose a model for COX biogenesis in which maturation of newly translated COX SUI is initially assisted by CtaG, a chaperone implicated in CuB site metallation, followed by the interaction with the heme chaperone Surf1c to populate the redox-active metal-heme centers in SUI. Only then the remaining smaller subunits are recruited to form the mature enzyme which ultimately associates with respiratory complexes I and III into supercomplexes.
In their post-traumatic course, trauma patients suffering from multiple injuries have a high risk for immune dysregulation, which may contribute to post-injury complications and late mortality. Monocytes as specific effector cells of the innate immunity play a crucial role in inflammation. Using their Pattern Recognition Receptors (PRRs), notably Toll-Like Receptors (TLR), the monocytes recognize pathogens and/or pathogen-associated molecular patterns (PAMPs) and organize their clearance. TLR2 is the major receptor for particles of gram-positive bacteria, and initiates their phagocytosis. Here, we investigated the phagocytizing capability of monocytes in a long-term porcine severe trauma model (polytrauma, PT) with regard to their TLR2 expression. Polytrauma consisted of femur fracture, unilateral lung contusion, liver laceration, hemorrhagic shock with subsequent resuscitation and surgical fracture fixation. After induction of PT, peripheral blood was withdrawn before (-1 h) and directly after trauma (0 h), as well as 3.5 h, 5.5 h, 24 h and 72 h later. CD14+ monocytes were identified and the expression levels of H(S)LA-DR and TLR2 were investigated by flow cytometry. Additionally, the phagocytizing activity of monocytes by applying S. aureus particles labelled with pHrodo fluorescent reagent was also assessed by flow cytometry. Furthermore, blood samples from 10 healthy pigs were exposed to a TLR2-neutralizing antibody and subsequently to S. aureus particles. Using flow cytometry, phagocytizing activity was determined. P below 0.05 was considered significant. The number of CD14+ monocytes of all circulating leukocytes remained constant during the observational time period, while the percentage of CD14+H(S)LA-DR+ monocytes significantly decreased directly, 3.5 h and 5.5 h after trauma. The percentage of TLR2+ expressing cells out of all monocytes significantly decreased directly, 3.5 h and 5.5 h after trauma. The percentage of phagocytizing monocytes decreased immediately and remained lower during the first 3.5 h after trauma, but increased after 24 h. Antagonizing TLR2 significantly decreased the phagocytizing activity of monocytes. Both, decreased percentage of activated as well as TLR2 expressing monocytes persisted as long as the reduced phagocytosis was observed. Moreover, neutralizing TLR2 led to a reduced capability of phagocytosis as well. Therefore, we assume that reduced TLR2 expression may be responsible for the decreased phagocytizing capacity of circulating monocytes in the early post-traumatic phase.
Aesthetic perception and judgement are not merely cognitive processes, but also involve feelings. Therefore, the empirical study of these experiences requires conceptualization and measurement of aesthetic emotions. Despite the long-standing interest in such emotions, we still lack an assessment tool to capture the broad range of emotions that occur in response to the perceived aesthetic appeal of stimuli. Elicitors of aesthetic emotions are not limited to the arts in the strict sense, but extend to design, built environments, and nature. In this article, we describe the development of a questionnaire that is applicable across many of these domains: the Aesthetic Emotions Scale (Aesthemos). Drawing on theoretical accounts of aesthetic emotions and an extensive review of extant measures of aesthetic emotions within specific domains such as music, literature, film, painting, advertisements, design, and architecture, we propose a framework for studying aesthetic emotions. The Aesthemos, which is based on this framework, contains 21 subscales with two items each, that are designed to assess the emotional signature of responses to stimuli’s perceived aesthetic appeal in a highly differentiated manner. These scales cover prototypical aesthetic emotions (e.g., the feeling of beauty, being moved, fascination, and awe), epistemic emotions (e.g., interest and insight), and emotions indicative of amusement (humor and joy). In addition, the Aesthemos subscales capture both the activating (energy and vitality) and the calming (relaxation) effects of aesthetic experiences, as well as negative emotions that may contribute to aesthetic displeasure (e.g., the feeling of ugliness, boredom, and confusion).
Background: The Objective Structured Clinical Examination (OSCE) is increasingly used at medical schools to assess practical competencies. To compare the outcomes of students at different medical schools, we introduced standardized OSCE stations with identical checklists.
Methods: We investigated examiner bias at standardized OSCE stations for knee- and shoulder-joint examinations, which were implemented into the surgical OSCE at five different medical schools. The checklists for the assessment consisted of part A for knowledge and performance of the skill and part B for communication and interaction with the patient. At each medical faculty, one reference examiner also scored independently to the local examiner. The scores from both examiners were compared and analysed for inter-rater reliability and correlation with the level of clinical experience. Possible gender bias was also evaluated.
Results: In part A of the checklist, local examiners graded students higher compared to the reference examiner; in part B of the checklist, there was no trend to the findings. The inter-rater reliability was weak, and the scoring correlated only weakly with the examiner’s level of experience. Female examiners rated generally higher, but male examiners scored significantly higher if the examinee was female.
Conclusions: These findings of examiner effects, even in standardized situations, may influence outcome even when students perform equally well. Examiners need to be made aware of these biases prior to examining.
In my paper I claim that methodology inspired by postcolonial theory not only unearths how Western international institutions perpetuate hegemonic truth claims, but that at the same time engaging in a “learning to learn from below” might sense irritations within these truth claims which can open up spaces to think beyond truth in a sense of a justice to come. (Derrida 2002) Since the (mis)understanding of knowledge production as truth finding is constitutive of both, the scientific and the legal discourse, the engagement in such research accordingly has the potential to unfold a twofold deconstructive force...
Was ist ein geographisches Bild? Darauf hat sicher jeder eine Antwort: Beim einen poppen im Kopf zunächst die Urlaubsfotos von der finnischen Schären-Küste oder aus Paris auf, die andere denkt an Satellitenaufnahmen des schwindenden Eisrandes der Arktis im GEO-Magazin oder an Claudia Kleinerts Wetterkarte in den Tagesthemen. Auf den ersten Blick scheint klar: alles Bilder, alles irgendwie geographisch.
Objective: Extracorporeal life support (ECLS) is a life-saving procedure used in the treatment of severe cardiogenic shock. Within this retrospective single centre study, we examined our experience in this critically ill patient cohort to assess outcomes and clinical parameters by comparison of ECLS with or without selective left ventricular decompression.
Methods: Between 2004 and 2014 we evaluated 48 adult patients with INTERMACS level 1 heart failure (age 49.7 ± 19.5 years), who received either central ECLS with (n = 20, 41.7%) or ECLS without (n = 28, 58.3%, including 10 peripheral ECLS) integrated left ventricular vent in our retrospective single centre trial.
Results: Follow up was 100% with a mean of 0.83 ± 1.85 years. Bridge to ventricular assist device was feasible in 29.2% (n = 14), bridge to transplant in 10.4% (n = 5) and bridge to recovery in 8.3% (n = 4). Overall 30-day survival was 37.5%, 6-month survival 27.1% and 1-year survival 25.0%. ECLS support with left ventricular decompression showed favourable 30-day survival compared to ECLS without left ventricular decompression (p = 0.034). Thirty-day as well as long-term survival did not differ between the subgroups (central ECLS with vent, ECLS without vent and peripheral ECLS without vent). Multivariate logistic regression adjusted for age and gender revealed ECLS without vent as independent factor influencing 30-day survival.
Conclusion: ECLS is an established therapy for patients in severe cardiogenic shock. Independent of the ECLS approach, 30-day mortality is still high but with superior 30-day survival for patients with ECLS and left ventricular venting. Moreover, by unloading the ventricle, left ventricular decompression may provide an important time window for recovery or further treatment, such as bridge to bridge or bridge to transplant.
Wer sich auf Spurensuche nach den Anfängen der modernen Sachliteratur für Kinder und Jugendliche begeben will, muss den Blick auf Strategien und Konzepte der Wissensvermittlung in der Literatur der Frühen Neuzeit richten. In der Zeit des 16. bis 18. Jahrhunderts entstand ausgehend von Innovationen der Pädagogik und Didaktik eine Wissen vermittelnde Kinder- und Jugendliteratur eigener Art. Die Methodik der Darstellung und adressatenspezifischen Zurichtung des Wissens in diesen Kinder- und Jugendbüchern akzentuiert zwar primär den omnipräsenten pädagogisch-didaktischen Anteil der Wissensvermittlung, lässt jedoch auch eine vornehmlich emblematisch-bildliche sowie eine wortbasierte, verbale Anschaulichkeit der Gestaltungsweise zu. Innovative Formen der Anschaulichkeit rücken den Zweck der Belehrung der Zöglinge in den Kontext einer kinder- und jugendorientierten Ästhetik der Wissensvermittlung. Diese dadurch entstehenden Formen der Anschaulichkeit sind es, die als Narrative in Bild und Wort erscheinen. Sie bilden das Inszenierte und das Ästhetische der Wissensvermittlung. ...
Der Zeitabschnitt zwischen 1815 bis 1848, der demokratisch-republikanische Vorfrühling, wird in der Literaturhistorik kontrovers gesehen und diskutiert. Denn zum Einen war da das Sich Reibende der Menschen an Verhältnissen, die zusehends durch ökonomischen Druck gekennzeichnet waren, und ihr daraus resultierendes Unwohlsein. Es gab etwas Gärendes, eine Unzufriedenheit, die sich Bahn brechen sollte und zur politischen Eruption von 1848 führte. Da war aber auch das Streben derjenigen, die man im Nachhinein unter dem Begriff Biedermeier subsumiert hat, nach der ländlichen Idylle und dem Rückzug ins Private. Es gab den Wunsch von vielen, der Kapitalismus, der am Horizont aufzuziehen begann, möge einen selbst noch verschonen, es möge einen Ausweg geben, und so reagiert auch der literarische Klassiker jener Epoche, Georg Büchners Figur Lenz, der einem wirklichen Menschen nachempfunden ist, verstört auf die zunehmende Kapitalisierung seiner Umgebung. Auch Lenz versucht, sich ihr zu entziehen, und Generationen von Schulkindern wurden Zeugen seiner Flucht ins Gebirge, die vergeblich bleiben musste. Lenz blieb letztlich nichts, als sich in eine Welt zu fügen, die nicht die seine war. Von nun an tat er: "[...] Alles wie es die Andern taten, es war aber eine entsetzliche Leere in ihm, er fühlte keine Angst mehr, kein Verlangen; sein Dasein war ihm eine notwendige Last. – So lebte er hin."
Gab es wirklich keine Möglichkeit, sich aus einer Entwicklung zu retten, die ein anderer Klassiker aus jenen Jahren folgendermaßen beschrieben hat: "Die Bourgeoisie," das sagen Karl Marx und Friedrich Engels im "Manifest der Kommunistischen Partei", das erstmals zu Beginn des revolutionären Jahres 1848 erschienen ist, "wo sie zur Herrschaft gekommen, hat alle feudalen, patriarchalischen, idyllischen Verhältnisse zerstört. Sie hat die buntscheckigen Feudalbande, die den Menschen an seinen natürlichen Vorgesetzten knüpften, unbarmherzig zerrissen und kein anderes Band zwischen Mensch und Mensch übriggelassen als das nackte Interesse, als die gefühllose bare Zahlung."
Welche Optionen gab es, auf "das nackte Interesse" und "die gefühllose bare Zahlung" zu reagieren? Georg Büchner hatte für die Revolte optiert und hatte sie gelebt, er hatte fliehen müssen und war jung verstorben. Andere versuchten, sich einen privaten Rückzugsort zu schaffen. Die Französin Louise Michel jedoch stand für einen dritten Weg, der allein der ihre war: Sie wollte sterben. Und ihren Todeswunsch hat sie mit großem Pathos verkündet.
Systemic sclerosis (SSc) is a rare multi-organ autoimmune disease characterized by progressive skin fibrosis. Inflammation, type 2 immunity, and fibrogenic processes are involved in disease development and may be affected by sphingolipids. However, details about early-stage pathophysiological mechanisms and implicated mediators remain elusive. The sphingolipid sphingosine-1-phosphate (S1P) is elevated in the sera of SSc patients, and its receptor S1P5 is expressed in skin tissue. Nevertheless, almost nothing is known about the dermatological contribution of S1P5 to inflammatory and pro-fibrotic processes leading to the pathological changes seen in SSc. In this study, we observed a novel effect of S1P5 on the inflammatory processes during low-dose bleomycin (BLM)-induced fibrogenesis in murine skin. By comparing 2-week-treated skin areas of wild-type (WT) and S1P5-deficient mice, we found that S1P5 is important for the transcriptional upregulation of the Th2 characteristic transcription factor GATA-3 under treatment-induced inflammatory conditions, while T-bet (Th1) and FoxP3 (Treg) mRNA expression was regulated independently of S1P5. Additionally, treatment caused a regulation of S1P receptor 1 and S1P receptor 3 mRNA as well as a regulation of long-chain ceramide profiles, which both differ significantly between the genotypes. Despite S1P5-dependent differences regarding inflammatory processes, similar macroscopic evidence of fibrosis was detected in the skin histology of WT and S1P5-deficient mice after 4 weeks of subcutaneous BLM treatment. However, at the earlier 2-week point in time, the mRNA data of pro-collagen type 1 and SMAD7 indicate a pro-fibrotic S1P5 contribution in the applied SSc mouse model. In conclusion, we propose that S1P5 plays a role as a novel modulator during the early phase of BLM-caused fibrogenesis in murine skin. An immediate relationship between dermal S1P5 expression and fibrotic processes leading to skin alterations, such as formative for SSc pathogenesis, is indicated but should be studied more profound in further investigations. Therefore, this study is an initial step in understanding the role of S1P5-mediated effects during early stages of fibrogenesis, which may encourage the ongoing search for new therapeutic options for SSc patients.
Invasive fungal infections are still an important cause of morbidity and mortality in immunocompromised patients such as patients suffering from hematological malignancies or patients undergoing hematopoietic stem cell transplantion. In addition, other populations such as human immunodeficiency virus-patients are at higher risk for invasive fungal infection. Despite the availability of new antifungal compounds and better supportive care measures, the fatality rate of invasive fungal infection remained unacceptably high. It is therefore of major interest to improve our understanding of the host–pathogen interaction to develop new therapeutic approaches such as adoptive immunotherapy. As experimental methodologies have improved and we now better understand the complex network of the immune system, the insight in the interaction of the host with the fungus has significantly increased. It has become clear that host resistance to fungal infections is not only associated with strong innate immunity but that adaptive immunity (e.g., T cells) also plays an important role. The antifungal activity of natural killer (NK) cells has been underestimated for a long time. In vitro studies demonstrated that NK cells from murine and human origin are able to attack fungi of different genera and species. NK cells exhibit not only a direct antifungal activity via cytotoxic molecules but also an indirect antifungal activity via cytokines. However, it has been show that fungi exert immunosuppressive effects on NK cells. Whereas clinical data are scarce, animal models have clearly demonstrated that NK cells play an important role in the host response against invasive fungal infections. In this review, we summarize clinical data as well as results from in vitro and animal studies on the impact of NK cells on fungal pathogens.
Impact of human mesenchymal stromal cells on antifungal host response against Aspergillus fumigatus
(2017)
Mesenchymal stromal cells (MSCs) are increasingly given as immunotherapy to hematopoietic stem cell transplant (HSCT) recipients with refractory graft-versus-host disease (GvHD). Whereas the immunosuppressive properties of MSCs seem to be beneficial in GvHD, there is, at the same time, major concern that MSCs increase the risk for infection. We therefore investigated the interplay of human MSCs with Aspergillus fumigatus and the impact of MSCs on different arms of the anti-Aspergillus host response in vitro. Although A. fumigatus hyphae increase mRNA levels of IL6 in MSCs, the extracellular availability of IL-6 and other pro-inflammatory cytokines remains unaffected. Human MSCs are able to phagocyte Aspergillus conidia, but phagocytosis of conidia is not associated with an alteration of the cytokine production by MSCs. In addition, human MSCs do not affect activation and function of A. fumigatus specific CD4+ T cells, and MSCs do not negatively impact the oxidative burst activity of phagocytes. Our in vitro data indicate that administration of human MSCs is not associated with a negative impact on the host response against A. fumigatus and that the fungus does not stimulate MSCs to increase the release of those cytokines which play a central role in the pathophysiology of GvHD.
In situ single particle analysis of ice particle residuals (IPRs) and out-of-cloud aerosol particles was conducted by means of laser ablation mass spectrometry during the intensive INUIT-JFJ/CLACE campaign at the high alpine research station Jungfraujoch (3580 m a.s.l.) in January–February 2013. During the 4-week campaign more than 70 000 out-of-cloud aerosol particles and 595 IPRs were analyzed covering a particle size diameter range from 100 nm to 3 µm. The IPRs were sampled during 273 h while the station was covered by mixed-phase clouds at ambient temperatures between −27 and −6 °C. The identification of particle types is based on laboratory studies of different types of biological, mineral and anthropogenic aerosol particles. The outcome of these laboratory studies was characteristic marker peaks for each investigated particle type. These marker peaks were applied to the field data. In the sampled IPRs we identified a larger number fraction of primary aerosol particles, like soil dust (13 ± 5 %) and minerals (11 ± 5 %), in comparison to out-of-cloud aerosol particles (2.4 ± 0.4 and 0.4 ± 0.1 %, respectively). Additionally, anthropogenic aerosol particles, such as particles from industrial emissions and lead-containing particles, were found to be more abundant in the IPRs than in the out-of-cloud aerosol. In the out-of-cloud aerosol we identified a large fraction of aged particles (31 ± 5 %), including organic material and secondary inorganics, whereas this particle type was much less abundant (2.7 ± 1.3 %) in the IPRs. In a selected subset of the data where a direct comparison between out-of-cloud aerosol particles and IPRs in air masses with similar origin was possible, a pronounced enhancement of biological particles was found in the IPRs.
Steilhänge der Mittelgebirge weisen eine kleinräumige standörtliche Vielfalt auf und wurden aufgrund ihrer exponierten Lage bereits frühzeitig durch den Menschen u. a. als Befestigungsanlage genutzt. Daraus resultierte häufig eine hohe floristische und vegetationskundliche Diversität mit hohem Naturschutzwert. Durch Umwelt- und Nutzungsveränderungen hat sich aber auch an diesen Standorten in den letzten Jahrzehnten ein starker Wandel vollzogen. Durch Auswertung alter Florenlisten und Vegetationsaufnahmen und durch aktuelle Erhebungen wollen wir die Vegetationszusammensetzung der Lengder Burg, eines Steilhangs auf Unterem Muschelkalk im südlichen Göttinger Wald (Süd-Niedersachsen, Deutschland), und ihre Veränderung aufzeigen und Rückschlüsse für die zukünftige Behandlung ziehen. Dazu wurden Angaben zur Gefäßpflanzenflora aus dem Zeitraum 1950 bis 1995 mit einer aktuellen floristischen Kartierung des Gesamtgebiets von 2016 verglichen. Die Vegetationszusammensetzung wurde anhand von 37 Vegetationsaufnahmen aus dem früheren Zeitraum harakterisiert. 29 dieser Flächen wurden 2009 bis 2016 erneut aufgenommen. Räumliche und zeitliche Unterschiede in der Diversität und Artenzusammensetzung wurden hinsichtlich verschiedener standörtlicher Parameter und ökologischer Artengruppen analysiert.
Die Vegetation lässt sich zwei Gruppen zuordnen: 1. Das Carici-Fagetum und seine Kontaktgesellschaften an südlich und westlich exponierten Steilhängen. 2. Das Hordelymo-Fagetum mit verschiedenen Ausbildungen auf dem Plateau und an flacheren Süd- und Nordhangbereichen. Im Carici-Fagetum ist ein deutlicher Diversitätsverlust und eine Zunahme in der Dominanzstruktur der Krautschicht zu erkennen, der im Vergleich der Aufnahmezeiträume auf eine zunehmende Homogenisierung der Vegetation hinweist. Zurückgegangen sind dabei besonders die typischen Kenn- und Trennarten dieser Waldgesellschaft bei gleichzeitiger Zunahme der Buche in der Verjüngung. Im Hordelymo-Fagetum bewirkt neben Gehölzen in der Strauch- und Krautschicht vor allem die Zunahme von Allium ursinum eine homogenere Artenzusammensetzung, jedoch ohne Diversitätsverlust. Neben Stickstoffeinträgen, dem Klimawandel sowie einem reduzierten Rehwild-Verbiss bedingt besonders der Nutzungswandel diese Veränderungen. Vor allem im Carici-Fagetum wirkte sich der Übergang zwischen früherer Nieder- und Mittelwald-Nutzung mit Waldweide über eine fast 100jährige Hochwald-Nutzung bis zum jetzigen Schutzwald stark aus. Gleichwohl weisen die steilen Hänge weiterhin einen hohen Anteil an Rote-Liste-Arten auf und tragen wesentlich zur hohen Biodiversität des Gebiets bei. Veränderungen in der Vegetation der Lengder Burg spiegeln die Veränderungen im Göttinger Wald insgesamt wider. Kleinflächige Offenhaltungsmaßnahmen zur Erhaltung wertvoller floristischer Elemente sind teilweise erfolgreich. Kleinwüchsige, lichtbedürftige Magerkeitszeiger verschwinden jedoch zunehmend aus den sich entwickelnden, hochwüchsigen Stauden-Säumen. In den benachbarten, unbewirtschafteten Hangbuchenwäldern sorgt die fehlende Nutzung nach Jahrhunderten der Auflichtung und Aushagerung für eine Sukzession in Richtung mesophilen Kalkbuchenwalds.
Three-dimensional multicellular aggregates such as spheroids provide reliable in vitro substitutes for tissues. Quantitative characterization of spheroids at the cellular level is fundamental. We present the first pipeline that provides three-dimensional, high-quality images of intact spheroids at cellular resolution and a comprehensive image analysis that completes traditional image segmentation by algorithms from other fields. The pipeline combines light sheet-based fluorescence microscopy of optically cleared spheroids with automated nuclei segmentation (F score: 0.88) and concepts from graph analysis and computational topology. Incorporating cell graphs and alpha shapes provided more than 30 features of individual nuclei, the cellular neighborhood and the spheroid morphology. The application of our pipeline to a set of breast carcinoma spheroids revealed two concentric layers of different cell density for more than 30,000 cells. The thickness of the outer cell layer depends on a spheroid’s size and varies between 50% and 75% of its radius. In differently-sized spheroids, we detected patches of different cell densities ranging from 5 × 105 to 1 × 106 cells/mm3. Since cell density affects cell behavior in tissues, structural heterogeneities need to be incorporated into existing models. Our image analysis pipeline provides a multiscale approach to obtain the relevant data for a system-level understanding of tissue architecture.
Dysregulation of lysophosphatidic acids in multiple sclerosis and autoimmune encephalomyelitis
(2017)
Bioactive lipids contribute to the pathophysiology of multiple sclerosis. Here, we show that lysophosphatidic acids (LPAs) are dysregulated in multiple sclerosis (MS) and are functionally relevant in this disease. LPAs and autotaxin, the major enzyme producing extracellular LPAs, were analyzed in serum and cerebrospinal fluid in a cross-sectional population of MS patients and were compared with respective data from mice in the experimental autoimmune encephalomyelitis (EAE) model, spontaneous EAE in TCR1640 mice, and EAE in Lpar2 -/- mice. Serum LPAs were reduced in MS and EAE whereas spinal cord LPAs in TCR1640 mice increased during the ‘symptom-free’ intervals, i.e. on resolution of inflammation during recovery hence possibly pointing to positive effects of brain LPAs during remyelination as suggested in previous studies. Peripheral LPAs mildly re-raised during relapses but further dropped in refractory relapses. The peripheral loss led to a redistribution of immune cells from the spleen to the spinal cord, suggesting defects of lymphocyte homing. In support, LPAR2 positive T-cells were reduced in EAE and the disease was intensified in Lpar2 deficient mice. Further, treatment with an LPAR2 agonist reduced clinical signs of relapsing-remitting EAE suggesting that the LPAR2 agonist partially compensated the endogenous loss of LPAs and implicating LPA signaling as a novel treatment approach.
Monoclonal antibodies (mAb) are promising therapeutics in multiple sclerosis and multiple new candidates have been developed, hence increasing the need for some agreement for preclinical mAb studies. We systematically analyzed publications of experimental autoimmune encephalomyelitis (EAE) studies showing effects of monoclonal antibodies. A PubMed search retrieved 570 records, out of which 122 studies with 253 experiments were eligible based on experimental design, number of animals and presentation of time courses of EAE scores. Analysis of EAE models, treatment schedules, single and total doses, routes of administration, and onset of treatment from pre-immunization up to 35 days after immunization revealed high heterogeneity. Total doses ranged from 0.1 to 360 mg/kg for observation times of up to 35 days after immunization. About half of experiments (142/253) used total doses of 10–70 mg/kg. Employing this range, we tested anti-Itga4 as a reference mAb at varying schedules and got no, mild or substantial EAE-score reductions, depending on the mouse strain and onset of the treatment. The result agrees with the range of outcomes achieved in 10 reported anti-Itga4 experiments. Studies comparing low and high doses of various mAbs or early vs. late onset of treatment did not reveal dose-effect or timing-effect associations, with a tendency towards better outcomes with preventive treatments starting within the first week after immunization. The systematic comparison allows for extraction of some “common” design characteristics, which may be helpful to further assess the efficacy of mAbs and role of specific targets in preclinical models of multiple sclerosis.
Die aus Amerika stammende, neophytische Kolumbianische Zwergwasserlinse Wolffia columbiana wurde in Europa erstmals im Jahr 2013 in Deutschland und den Niederlanden nachgewiesen. Daraufhin wurden weitere 11 Freilandvorkommen von Wolffia aus Deutschland (Nordrhein-Westfalen, Hessen und Rheinland-Pfalz), den Niederlanden und Polen überprüft. Bei 10 der insgesamt 13 untersuchten Proben handelte es sich um Wolffia columbiana, darunter alle 8 bislang untersuchten Vorkommen aus Deutschland. Lediglich bei 3 Freilandproben aus den Niederlanden und Polen handelte es sich um die einheimische Wolffia arrhiza. Der Neophyt scheint also durchaus weiter verbreitet zu sein als gedacht. Die Unterscheidung beider Arten ist nicht ganz leicht, die Unterscheidungsmerkmale werden vorgestellt. Die Vorkommen von Wolffia in Europa sollten überprüft werden, um zu klären, wie viele Vorkommen von Wolffia arrhiza es überhaupt noch gibt, und bei wie vielen Vorkommen es sich tatsächlich um die neophytische Wolffia columbiana oder andere neophytische Wolffia-Arten handelt.
In cancer medicine, particularly in drug research and development, structural changes in professionalism can be observed as examples. This field is characterized by a strong tension between social expectations concerning the control of existential risks to health, on the one hand, and strong commercial interests of a shareholder value-driven industry, on the other hand. Based on a qualitative empirical analysis, two subfields within the field of cancer medicine are reconstructed. One of these subfields—colon cancer therapy—could be interpreted as representing a renewal of the knowledge-power nexus. The pattern of the other subfield—brain tumour research—refers to a much more vulnerable professionalism. Both fields are characterized by development in professional work, which could be described with the hybridization concept. Therefore, the contrast between the two empirical examples presented still challenges the theoretical interpretation of contemporary professionalism.
Editorial
(2017)
Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a pleiotropic, Th17-derived cytokine thought to critically contribute to the pathogenesis of diverse autoimmune diseases, including rheumatoid arthritis and psoriasis. Treatment with monoclonal antibodies that block GM-CSF activity is associated with favorable therapeutic effects in patients with rheumatoid arthritis. We evaluated the role of GM-CSF as a potential target for therapeutic interference in psoriasis using a combined pharmacologic and genetic approach and the mouse model of imiquimod-induced psoriasiform dermatitis (IMQPD). Neutralization of murine GM-CSF by an anti-GM-CSF antibody ameliorated IMQPD. In contrast, genetic deficiency in GM-CSF did not alter the course of IMQPD, suggesting the existence of mechanisms compensating for chronic, but not acute, absence of GM-CSF. Further investigation uncovered an alternative pathogenic pathway for IMQPD in the absence of GM-CSF characterized by an expanded plasmacytoid dendritic cell population and release of IFNα and IL-22. This pathway was not activated in wild-type mice during short-term anti-GM-CSF treatment. Our investigations support the potential value of GM-CSF as a therapeutic target in psoriatic disease. The discovery of an alternative pathogenic pathway for psoriasiform dermatitis in the permanent absence of GM-CSF, however, suggests the need for monitoring during therapeutic use of long-term GM-CSF blockade.
Ice nucleating particles over the eastern mediterranean measured by unmanned aircraft systems
(2017)
During an intensive field campaign on aerosol, clouds, and ice nucleation in the Eastern Mediterranean in April 2016, we measured the abundance of ice nucleating particles (INPs) in the lower troposphere from unmanned aircraft systems (UASs). Aerosol samples were collected by miniaturized electrostatic precipitators onboard the UASs at altitudes up to 2.5 km. The number of INPs in these samples, which are active in the deposition and condensation modes at temperatures from −20 to −30 °C, were analyzed immediately after collection on site using the ice nucleus counter FRIDGE (FRankfurt Ice nucleation Deposition freezinG Experiment). During the 1-month campaign, we encountered a series of Saharan dust plumes that traveled at several kilometers' altitude. Here we present INP data from 42 individual flights, together with aerosol number concentrations, observations of lidar backscattering, dust concentrations derived by the dust transport model DREAM (Dust Regional Atmospheric Model), and results from scanning electron microscopy. The effect of the dust plumes is reflected by the coincidence of INPs with the particulate matter (PM), the lidar signal, and the predicted dust mass of the model. This suggests that mineral dust or a constituent related to dust was a major contributor to the ice nucleating properties of the aerosol. Peak concentrations of above 100 INPs std L−1 were measured at −30 °C. The INP concentration in elevated plumes was on average a factor of 10 higher than at ground level. Since desert dust is transported for long distances over wide areas of the globe predominantly at several kilometers' altitude, we conclude that INP measurements at ground level may be of limited significance for the situation at the level of cloud formation.
A high proportion of patients with breast cancer develop bone metastases, yet data on routine treatment with bone-targeted agents (BTA) are rare. We report real-life outcome data of patients with breast cancer metastasised to the bone treated by office-based oncologists in Germany.
The ongoing, prospective, multicentre, population-based cohort study Tumour Registry Breast Cancer (TMK) was started in 2007 in 140 centres across Germany.
This interim analysis of 1094 patients with bone metastases revealed differences among the tumour subtypes: at start of first-line therapy, 36% of the patients with hormone receptor (HR)-positive and only 20% of the patients with HR-negative tumours presented with bone-only metastasis. The majority of patients with bone metastases (89%, n = 976) received BTA therapy. In 2014–2015, 37% of the patients received the bisphosphonate zoledronic acid and 36% the antibody denosumab. Median duration of BTA therapy was 20 months (interquartile range 31.5 months), starting a median of 3 weeks after diagnosis of bone metastases, and ending a median of 7 weeks before death. The median overall survival (OS) also varied among the types of metastasis at start of first-line therapy ranging from 54 months (95% confidence interval [CI] 37.6–70.8), 38 months (95% CI 29.4–44.2) to 28 months (95% CI 24.2–31.0) for patients with bone-only metastases, non-visceral with or without bone metastases and visceral with or without bone metastases respectively.
We show that choice and duration of BTA therapies are in conformity with guidelines applicable in Germany. To our knowledge, this is the first presentation of data on incidence, metastatic pattern, treatment and survival of patients with bone metastases in routine practice.
NADPH oxidases of the Nox family are important enzymatic sources of reactive oxygen species (ROS) in the cardiovascular system. Of the 7 members of the Nox family, at least three depend for their activation on specific cytosolic proteins. These are p47phox and its homologue NoxO1 and p67phox and its homologue NoxA1. Also the Rho-GTPase Rac is important but as this protein has many additional functions, it will not be covered here. The Nox1 enzyme is preferentially activated by the combination of NoxO1 with NoxA1, whereas Nox2 gains highest activity with p47phox together with p67phox. As p47phox, different to NoxO1 contains an auto inhibitory region it has to be phosphorylated prior to complex formation. In the cardio-vascular system, all cytosolic Nox proteins are expressed but the evidence for their contribution to ROS production is not well established. Most data have been collected for p47phox, whereas NoxA1 has basically not yet been studied. In this article the specific aspects of cytosolic Nox proteins in the cardiovascular system with respect to Nox activation, their expression and their importance will be reviewed. Finally, it will be discussed whether cytosolic Nox proteins are suitable pharmacological targets to tamper with vascular ROS production.
T lymphocytes against tumor-specific mutated neoantigens can induce tumor regression. Also, the size of the immunogenic cancer mutanome is supposed to correlate with the clinical efficacy of checkpoint inhibition. Herein, we studied the susceptibility of tumor cell lines from lymph node metastases occurring in a melanoma patient over several years towards blood-derived, neoantigen-specific CD8+ T cells. In contrast to a cell line established during early stage III disease, all cell lines generated at later time points from stage IV metastases exhibited partial or complete loss of HLA class I expression. Whole exome and transcriptome sequencing of the four tumor lines and a germline control were applied to identify expressed somatic single nucleotide substitutions (SNS), insertions and deletions (indels). Candidate peptides encoded by these variants and predicted to bind to the patient’s HLA class I alleles were synthesized and tested for recognition by autologous mixed lymphocyte-tumor cell cultures (MLTCs). Peptides from four mutated proteins, HERPUD1G161S, INSIG1S238F, MMS22LS437F and PRDM10S1050F, were recognized by MLTC responders and MLTC-derived T cell clones restricted by HLA-A*24:02 or HLA-B*15:01. Intracellular peptide processing was verified with transfectants. All four neoantigens could only be targeted on the cell line generated during early stage III disease. HLA loss variants of any kind were uniformly resistant. These findings corroborate that, although neoantigens represent attractive therapeutic targets, they also contribute to the process of cancer immunoediting as a serious limitation to specific T cell immunotherapy.
According to a proposal by 't Hooft, information loss introduced by constraints in certain classical dissipative systems may lead to quantization. This scheme can be realized within the Bateman model of two coupled oscillators, one damped and one accelerated. In this paper we analyze the links of this approach to effective Hamiltonians where the environmental degrees of freedom do not appear explicitly but their effect leads to the same friction force appearing in the Bateman model. In particular, it is shown that by imposing constraints, the Bateman Hamiltonian can be transformed into an effective one expressed in expanding coordinates. This one can be transformed via a canonical transformation into Caldirola and Kanai's effective Hamiltonian that can be linked to the conventional system-plus-reservoir approach, for example, in a form used by Caldeira and Leggett.
Der französische Frühsozialist Pierre-Joseph Proudhon (1809-1865) gilt unumstritten als der "Vater der Anarchie". Auf ihn geht die positive Umdeutung des Begriffs "Anarchismus" zurück. Sein Einfluss und seine Bedeutung für die Entstehung des sog. wissenschaftlichen Sozialismus und auf die anarchistische Bewegung in Deutschland sind von nicht zu unterschätzender Bedeutung. Er hat darüber hinaus, mehr noch als seine Vorläufer Claude-Henri Saint-Simon und Charles Fourier, größeren Einfluss auf den deutschen Diskurs über Sozialismus gehabt. Der Historiker Max Nettlau erklärte über seine deutsche Rezeption:
Proudhon wurde in Deutschland sehr beachtet, wo damals die radikale Philosophie um Arnold Ruge und Ludwig Feuerbach sich nach einer folgerichtigen Weiterentwicklung auf allen Gebieten sehnte, also dem die Theologie negierenden philosophischen Radikalismus, den den Staat negierenden politischen Radikalismus und die bestehenden Eigentumsverhältnisse negierenden ökonomischen Radikalismus zur Seite zu setzen bereit war.
Als Zeitraum für die Untersuchung seiner Rezeption in Deutschland bietet sich das Vierteljahrhundert von 1840, dem Erscheinungsjahr von Proudhons Studie „Qu’est-ce que la propriété?“, bis zum Jahr 1865, in dem er starb, an.
We present first data on centrality dependent K+, K− and ϕ production in Au+Au collisions at a kinetic beam energy of 1.23A GeV measured with HADES. We observe no significant increase of the K+/K− and ϕ/K− multiplicity ratios with centrality of the collision. The measured ϕ/K− ratio is found to be larger than results at higher energies. The significant ϕ feed-down contribution to the K− yield substantially softens the measured transverse mass spectrum of K−, explaining its lower observed effective temperature in comparison to the one of K+.
The present article encompasses the bibliography of Prof. Horst Schuller, researcher, literature Historian and translator.
This article refers to a number of translators, who translate from German to Romanian and also to the bibliography of their translations Georg Aescht, Theochar Alexi, Verona Bratesch (Brateş), Maria Dima, Sextil-Iosif Puşcariu, Daniel Friedrich Rhein, Arnold Roth, Christian W. Schenk
The RNA-chaperone Hfq catalyses the annealing of bacterial small RNAs (sRNAs) with target mRNAs to regulate gene expression in response to environmental stimuli. Hfq acts on a diverse set of sRNA-mRNA pairs using a variety of different molecular mechanisms. Here, we present an unusual crystal structure showing two Hfq-RNA complexes interacting via their bound RNA molecules. The structure contains two Hfq6:A18 RNA assemblies positioned face-to-face, with the RNA molecules turned towards each other and connected via interdigitating base stacking interactions at the center. Biochemical data further confirm the observed interaction, and indicate that RNA-mediated contacts occur between Hfq-RNA complexes with various (ARN)X motif containing RNA sequences in vitro, including the stress response regulator OxyS and its target, fhlA. A systematic computational survey also shows that phylogenetically conserved (ARN)X motifs are present in a subset of sRNAs, some of which share similar modular architectures. We hypothesise that Hfq can co-opt RNA-RNA base stacking, an unanticipated structural trick, to promote the interaction of (ARN)X motif containing sRNAs with target mRNAs on a "speed-dating" fashion, thereby supporting their regulatory function.
Green tea (GT) and green tea extracts (GTE) have been postulated to decrease cancer incidence. In vitro results indicate a possible effect; however, epidemiological data do not support cancer chemoprevention. We have performed a PubMED literature search for green tea consumption and the correlation to the common tumor types lung, colorectal, breast, prostate, esophageal and gastric cancer, with cohorts from both Western and Asian countries. We additionally included selected mechanistical studies for a possible mode of action. The comparability between studies was limited due to major differences in study outlines; a meta analysis was thus not possible and studies were evaluated individually. Only for breast cancer could a possible small protective effect be seen in Asian and Western cohorts, whereas for esophagus and stomach cancer, green tea increased the cancer incidence, possibly due to heat stress. No effect was found for colonic/colorectal and prostatic cancer in any country, for lung cancer Chinese studies found a protective effect, but not studies from outside China. Epidemiological studies thus do not support a cancer protective effect. GT as an indicator of as yet undefined parameters in lifestyle, environment and/or ethnicity may explain some of the observed differences between China and other countries.
Das im zweijährigen Turnus stattfindende International Symposium on Place Names (ISPN) wurde unter Leitung von Prof. Herman Breyer ausgerichtet.
In zahlreichen Vorträgen wurde herausgearbeitet, welche hohe Bedeutung die Namengebung für Straßen, Schulen und andere öffentliche Einrichtungen für die Identitätsstiftung besitzen kann. Ein weiterer Aspekt, der in vielfältiger Weise diskutiert wurde, ist die Relevanz von Toponymen als Teil des historischen Erbes.
The mammalian thalamocortical system generates intrinsic activity reflecting different states of excitability, arising from changes in the membrane potentials of underlying neuronal networks. Fluctuations between these states occur spontaneously, regularly, and frequently throughout awake periods and influence stimulus encoding, information processing, and neuronal and behavioral responses. Changes of pupil size have recently been identified as a reliable marker of underlying neuronal membrane potential and thus can encode associated network state changes in rodent cortex. This suggests that pupillometry, a ubiquitous measure of pupil dilation in cognitive neuroscience, could be used as an index for network state fluctuations also for human brain signals. Considering this variable may explain task-independent variance in neuronal and behavioral signals that were previously disregarded as noise.
Cortex-wide BOLD fMRI activity reflects locally-recorded slow oscillation-associated calcium waves
(2017)
Spontaneous slow oscillation-associated slow wave activity represents an internally generated state which is characterized by alternations of network quiescence and stereotypical episodes of neuronal activity - slow wave events. However, it remains unclear which macroscopic signal is related to these active periods of the slow wave rhythm. We used optic fiber-based calcium recordings of local neural populations in cortex and thalamus to detect neurophysiologically defined slow calcium waves in isoflurane anesthetized rats. The individual slow wave events were used for an event-related analysis of simultaneously acquired whole-brain BOLD fMRI. We identified BOLD responses directly related to onsets of slow calcium waves, revealing a cortex-wide BOLD correlate: the entire cortex was engaged in this specific type of slow wave activity. These findings demonstrate a direct relation of defined neurophysiological events to a specific BOLD activity pattern and were confirmed for ongoing slow wave activity by independent component and seed-based analyses.
Am 25. und 26. November 2016 fand am Germanistischen Institut der Westfälischen Wilhelms-Universität die vom Autor dieses Berichts organisierte Tagung „Historische Wortbildung. Theorie – Methoden – Perspektiven“ statt. Dabei sollte vor allem die diachrone Wortbildungsforschung zum Deutschen Berücksichtigung finden, eine Forschungsrichtung also, die nach wie vor eine Forschungslücke darstellt. Die heute zur Verfügung stehenden synchronen Beschreibungen der Wortbildung früherer Sprachstufen sowie die Digitalisierung historischer Textbestände und deren Implementierung in komplexe Datenbanken (z. B. des Deutschen Textarchivs2, des Altdeutschen Referenzkorpus3, etc.) bieten der diachron-historischen Wortbildungsforschung neue Möglichkeiten, die es nun zu nutzen gilt.
Can variances of latent variables be scaled in such a way that they correspond to eigenvalues?
(2017)
The paper reports an investigation of whether sums of squared factor loadings obtained in confirmatory factor analysis correspond to eigenvalues of exploratory factor analysis. The sum of squared factor loadings reflects the variance of the corresponding latent variable if the variance parameter of the confirmatory factor model is set equal to one. Hence, the computation of the sum implies a specific type of scaling of the variance. While the investigation of the theoretical foundations suggested the expected correspondence between sums of squared factor loadings and eigenvalues, the necessity of procedural specifications in the application, as for example the estimation method, revealed external influences on the outcome. A simulation study was conducted that demonstrated the possibility of exact correspondence if the same estimation method was applied. However, in the majority of realized specifications the estimates showed similar sizes but no correspondence.
Microtubule-targeting agents (MTAs) are the most widely used chemotherapeutic drugs. Pretubulysin (PT), a biosynthetic precursor of the myxobacterial tubulysins, was recently identified as a novel MTA. Besides its strong anti-tumoral activities, PT attenuates tumor angiogenesis, exerts anti-vascular actions on tumor vessels and decreases cancer metastasis formation in vivo. The aim of the present study was to analyze the impact of PT on the interaction of endothelial and tumor cells in vitro to gain insights into the mechanism underlying its anti-metastatic effect. The influence of PT on tumor cell adhesion and transmigration onto/through the endothelium as well as its influence on cell adhesion molecules and the chemokine system CXCL12/CXCR4 was investigated. Treatment of human endothelial cells with PT increased the adhesion of breast cancer cells to the endothelial monolayer, whereas their transmigration through the endothelium was strongly reduced. Interestingly, the PT-induced upregulation of ICAM-1, VCAM-1 and CXCL12 were dispensable for the PT-evoked tumor cell adhesion. Tumor cells preferred to adhere to collagen exposed within PT-triggered endothelial gaps via β1-integrins on the tumor cell surface. Taken together, our study provides, at least in part, an explanation for the anti-metastatic potential of PT.
FinTech as enabler of entrepreneurship and growth in the EU : interview with Joachim Schwerin
(2017)
A balanced sphingolipid rheostat is indispensable for dendritic cell function and survival and thus initiation of an immune response. Sphingolipid levels are dynamically maintained by the action of sphingolipid enzymes of which sphingosine kinases, S1P phosphatases (SGPP-1/2) and S1P lyase (SGPL-1), are pivotal in the balance of S1P and sphingosine levels. In this study, we present that SGPP-1 and SGPL-1 are regulated in inflammatory dendritic cells and contribute to S1P fate. TLR-dependent activation caused SGPL-1 protein downregulation with subsequent decrease of enzymatic activity by two-thirds. In parallel, confocal fluorescence microscopy revealed that endogenous SGPP-1 was expressed in nuclei of naive dendritic cells and was translocated into the cytoplasmatic compartment upon inflammatory stimulation resulting in dephosphorylation of S1P. Mass spectrometric determination showed that a part of the resulting sphingosine was released from the cell, increasing extracellular levels. Another route of diminishing intracellular S1P was possibly taken by its export via ATP-binding cassette transporter C1 which was upregulated in array analysis, while the S1P transporter, spinster homolog 2, was not relevant in dendritic cells. These investigations newly describe the sequential expression and localization of the endogenous S1P regulators SGPP-1 and SGPL-1 and highlight their contribution to the sphingolipid rheostat in inflammation.
Previous studies detected an influence of urban characteristics on song traits in passerine birds, that is, song adjustments to ambient noise in urban areas. Several studies already described the effect of weather conditions on the behavior of birds, but not the effect on song traits. We investigate, if song trait variability changes along a continuous urbanity gradient in Frankfurt am Main, Germany. We examined, for the first time on a larger scale, the influence of weather on song parameters. We made song recordings of three common passerine species: the blue and great tit (Cyanistes caeruleus (Linnaeus, 1758) and Parus major Linnaeus, 1758) and the European blackbird (Turdus merula Linnaeus, 1758). We measured different song traits and performed statistical analyses and modeling on a variety of variables—among them urbanity and weather parameters. Remarkably, we found only few cases of a significant influence of urbanity parameters on song traits. The influence of weather parameters (air pressure, atmospheric humidity, air and soil temperatures) on song traits was highly significant. Birds in Frankfurt face high noise pollution and might show different adaptations to high noise levels. The song trait variability of the investigated species is affected more by weather conditions than by urban characteristics in Frankfurt. However, the three species react differently to specific weather parameters. Smaller species seem to be more affected by weather than larger species.
Organized by Sabine Schulte im Walde (University of Stuttgart) and Eva Smolka (University of Konstanz) as part of the 39th Annual Conference of the German Linguistic Society (DGfS) held at the Saarland University in Saarbrücken, Germany, the workshop aimed “to shed light on the interaction of constituent properties and compound transparency across languages and disciplines integrating linguistic, psycholinguistic, corpus-based and computational studies”. The workshop brought together researchers from linguistics, psycholinguistics, and natural language processing and comprised 11 contributed talks, framed by two invited talks by Gary Libben and Marco Marelli. Most of the slides are available from the workshop’s homepage at “http://www.ims.uni-stuttgart.de/events/dgfs-mwe-17/program.html”.
TechQuartier to boost the start-up scene in Frankfurt am Main : interview with Sebastian Schäfer
(2017)
Interview with Sebastian Schäfer, Managing Director TechQuartier, Frankfurt
A randomised, double-blind, placebo-controlled trial of trichuris suis ova in active crohn's disease
(2017)
BACKGROUND AND AIMS To investigate the efficacy and safety of three different dosages of embryonated, viable eggs of Trichuris suis [TSO] versus placebo for induction of remission in mildly-to-moderately active ileocolonic, uncomplicated Crohn's disease [CD].
METHODS Adults with active CD [n = 252] randomly received six fortnightly doses of 250, 2500, or 7500 TSO/15 ml suspension/day [TSO 250, TSO 2500, TSO 7500], or 15 ml placebo solution/day, in a double-blind fashion, with 4 weeks' follow-up. Primary endpoint was the rate of clinical remission [Crohn's Disease Activity Index [CDAI] < 150] at end of treatment, ie at Week 12 or withdrawal. Secondary endpoints included the course of clinical remission, rate of clinical response, change in CDAI, change in markers of inflammation, mucosal healing, and Physician's Global Assessment.
RESULTS Clinical remission at Week 12 occurred in 38.5%, 35.2%, and 47.2% of TSO 250, TSO 2500, and TSO 7500 patients, respectively, and in 42.9% of placebo recipients. TSO induced a dose-dependent immunological response. There was no response regarding laboratory markers of inflammation. Other secondary efficacy variables also showed no advantage of TSO over placebo for treatment of active CD. Administration of TSO did not result in any serious adverse drug reaction. Review of non-serious suspected adverse drug reactions following TSO did not reveal any safety concerns.
CONCLUSIONS Administration of 250-7500 TSO fortnightly over 12 weeks was safe and showed a dose-dependent immunological response, but no TSO dose showed a clinically relevant effect over placebo for induction of clinical remission or response in mildly-to-moderately active, ileocolonic CD.