TLR2 and TLR4 agonists induce production of the vasoactive peptide endothelin-1 by human dendritic cells

Endothelin-1 (ET-1) is mainly secreted by endothelial cells and acts as a potent vasoconstrictor. In addition ET-1 has also been shown to have pleiotropic effects on a variety of other systems including adaptive immunity. There are two main ET-1 receptors, ET(A) and ET(B), which have different tissue and functional distributions. Dendritic cells (DC) are pivotal antigen-presenting cells linking the innate with the adaptive immune system. DC are sentinels expressing pattern-recognition receptors, e.g. the toll-like receptors (TLR) for detecting danger signals released from pathogens or tissue injury. Here we show for the first time that stimulation of human monocyte-derived DC with exogenous as well as endogenous selective TLR4 and TLR2 agonists induces the production of ET-1 in a dose- and time-dependent manner. 'Alternative' activation of DC in the presence of 1alpha,25-dihydroxyvitamin D(3) results in a marked potentiation of the endothelin response, whereas prostaglandin E(2) or dexamethasone do not increase ET-1 production. Furthermore, chetomin, an inhibitor of the transcription factor hypoxia-inducible factor 1alpha (HIF-1alpha), prevents TLR-mediated secretion of ET-1. Surprisingly, stimulation of human monocytes with LPS does not lead to secretion of detectable amounts of ET-1. These results suggest a role of ET-1 as an important player in human DC biology and innate immunity in general.

Beta1 integrin deficiency results in multiple abnormalities of the knee joint

The lack of beta1 integrins on chondrocytes leads to severe chondrodysplasia associated with high mortality rate around birth. To assess the impact of beta1 integrin-mediated cell-matrix interactions on the function of adult knee joints, we conditionally deleted the beta1 integrin gene in early limb mesenchyme using the Prx1-cre transgene. Mutant mice developed short limbed dwarfism and had joint defects due to beta1 integrin deficiency in articular regions. The articular cartilage (AC) was structurally disorganized, accompanied by accelerated terminal differentiation, altered shape, and disrupted actin cytoskeleton of the chondrocytes. Defects in chondrocyte proliferation, cytokinesis, and survival resulted in hypocellularity. However, no significant differences in cartilage erosion, in the expression of matrix-degrading proteases, or in the exposure of aggrecan and collagen II cleavage neoepitopes were observed between control and mutant AC. We found no evidence for disturbed activation of MAPKs (ERK1/2, p38, and JNK) in vivo. Furthermore, fibronectin fragment-stimulated ERK activation and MMP-13 expression were indistinguishable in control and mutant femoral head explants. The mutant synovium was hyperplastic and frequently underwent chondrogenic differentiation. beta1-null synoviocytes showed increased proliferation and phospho-focal adhesion kinase expression. Taken together, deletion of beta1 integrins in the limb bud results in multiple abnormalities of the knee joints; however, it does not accelerate AC destruction, perturb cartilage metabolism, or influence intracellular MAPK signaling pathways.

Increasing Quality in large scale University Courses

Quality of education should be stable or permanently increased – even if the number of students rises. Quality of education is often related to possibilities for active learning and individual facilitation. This paper deals with the question how high-quality learning within oversized courses could be enabled and it presents the approach of e-flashcards that enables active learning and individual facilitation within large scale university courses.

A compilation of Western European terrestrial records 60–8 ka BP: towards an understanding of latitudinal climatic gradients

Terrestrial records of past climatic conditions, such as lake sediments and speleothems, provide data of great importance for understanding environmental changes. However, unlike marine and ice core records, terrestrial palaeodata are often not available in databases or in a format that is easily accessible to the non-specialist. As a consequence, many excellent terrestrial records are unknown to the broader palaeoclimate community and are not included in compilations, comparisons, or modelling exercises. Here we present a compilation of Western European terrestrial palaeo-records covering, entirely or partially, the 60–8-ka INTIMATE time period. The compilation contains 56 natural archives, including lake records, speleothems, ice cores, and terrestrial proxies in marine records. The compilation is limited to include records of high temporal resolution and/or records that provide climate proxies or quantitative reconstructions of environmental parameters, such as temperature or precipitation, and that are of relevance and interest to a broader community. We briefly review the different types of terrestrial archives, their respective proxies, their interpretation and their application for palaeoclimatic reconstructions. We also discuss the importance of independent chronologies and the issue of record synchronization. The aim of this exercise is to provide the wider palaeo-community with a consistent compilation of high-quality terrestrial records, to facilitate model-data comparisons, and to identify key areas of interest for future investigations. We use the compilation to investigate Western European latitudinal climate gradients during the deglacial period and, despite of poorly constrained chronologies for the older records, we summarize the main results obtained from NW and SW European terrestrial records before the LGM.

Can stable isotope analysis and tooth histology assist in detecting stillbirth? An approach using neonatal remains from the Roman settlement Studen Petinesca

Infant burials in Roman settlements are a common observation. Even though ancient authors provide information many questions remain uncertain. For instance, the burial ritual for stillbirth and infanticide neonates is not specifically mentioned. This study therefore aimed to investigate the application of stable nitrogen (δ15N) and carbon (δ13C) isotopes from neonatal bone collagen in differentiating between a breastfeeding signal and stillbirth or a short survival of less than ten days. For this purpose collagen of 11 human and 14 non-human bones from the Roman settlement Petinesca (1st - 3rd century AD, Switzerland) was extracted and analysed for δ15N and δ13C. Tooth histology was performed for the central incisor and canine of the right mandible in order to investigate the presence of a neonatal line. According to the length of the long bones the age varied between 8.5 lunar months to 2 months ex utero. The stable isotope results provided a breastfeeding signal for all except one individual where the breastfeeding signal was absent. The tooth histological analysis of this individual exhibited no neonatal line. It is concluded that stable isotope analysis could indicate stillbirth or a short survival after birth. The tooth histology confirmed the stable isotope results. Furthermore, this might indicate that the burial ritual did not differentiate between stillbirth and neonates, who died within the time span stated by ancient authors of up to 40 days of age or the appearance of teeth. However, for further justifications additional research is going to be conducted.

Na 1 Nachlass Max Horkheimer, 96 - Korrespondenzen u.a. mit Jürgen Habermas (p. III 6, 1-421)

5 Briefe mit Antwort an Inga Haag, 1951-1955; 1 Brief mit Antwort von Jürgen Habermas an Max Horkheimer, 1955; 1 Brief von Ministerialrat i. R. Theodor Häbich an Max Horkheimer, 1957; 2 Briefe mit Antwort von cand. phil. Walter Hähnle an Max Horkheimer, 1955, 1957; 1 Brief mit Antwort von Sekretärin Jutta Hagen an Max Horkheimer, 1956; 1 Dissertationsauszug von Volker Freiherr von Hagen, 1954; 1 Brief mit Antwort von Julia Hagenbucher an Max Horkheimer, 1951/1952; 1 Entwurf zu einem Gratulationsschreiben von Max Horkheimer an Professor Otto Hahn, ohne Jahr; 2 Drucksachen von Obermagistratsrat Julius Hahn, 1953, 1955; 1 Brief mit Antwort von Theodor W. Adorno, von Dr. Hans Hahn an Max Horkheimer, 1952; 1 Brief von Theodor W. Adorno an Dr. Hans Hahn, 1952; 1 Danksagung von Rabbi Hugo Hahn, 1955; 3 Briefe mit Antwort von Paul Hahn an Max Horkheimer, 1951-1958; 1 Brief von Max Horkheimer an die Gebrüder Haldy, 1952; 1 Brief mit Antwort und Beilage von Professor George W. F. Hallgarten an Max Horkheimer, 1950; 1 Rundschreiben von Arzt und Psychotherapeut Hans Hammer, 1957; 1 Brief von Max Horkheimer an Margarete Hampf-Solm, 1955; 1 Brief mit Antwort von Professor Eduardo Hamuy an Max Horkheimer, 1952; 1 Brief von der Stadtärztin Dr. med. Carola Hannappel an Max Horkheimer, 1951; 1 Brief von Hansenmeister an Max Horkheimer, 1951; 1 Brief mit Antwort und Beilage von der Buchhandlung Ludwig Häntzschel an Max Horkheimer, 1958; 1 Brief von Professor Frederick Harris Harbison an Max Horkheimer, 1952; 3 Briefe mit Antwort von Robert Harcourt an Max Horkheimer, 1958; 1 Brief von Karl Hardach an Max Horkheimer, 1957; 1 Brief mit Antwort von Emilie Harlacher an Max Horkheimer, 1952; 1 Drucksache mit Antwort von Oberkirchenrat Otto L. A. von Harling an Max Horkheimer, 1955; 1 Brief mit Antwort von Gertrud Harms an Max Horkheimer, 1955; 2 Brief mit Antwort von Professor Wolfgang Hartke an Max Horkheimer, 1954-1956; 2 Briefe mit antwort von Max Horkheimer an Senator Georg Hartmann, 1951, 1954; 3 briefe mit Antwort und Beilage von Ökonom Heinz Hartmann an Max Horkheimer, 1956-1958; 1 Brief mit Antwort von Professor Wilbert E. Moore an Max Horkheimer, 1957; 3 Briefe mit Antwort und Beilage von Dr. phil. Leo Hartmann an Max Horkheimer, 1957-1858; 1 Brief mit Antowort von Dr. phil. Eckardt Mesch an Max Horkheimer, 1957; 1 Brief mit Antwort von Luzie Hatch an Max Horkheimer, 1954; 1 Brief von Max Horkheimer an den Direktor H. W. Haupt, 1950; 1 Drucksache von Haus Schwalbach, 1951; 4 Briefe mit Antwort von Professor Gottfried und Ellen Hausmann an Max Horkheimer, 1951-1958; 6 Briefe mit Antwort von Eva Haussner an Max Horkheimer, 1957, 1958; 1 Brief mit Antwort von Professor Robert J. Havighurst an Max Horkheimer, 1951; 1 Brief mit Beilage von Herbert Hax an Max Horkheimer, 1955; 2 Briefe mit Antwort und Beilage von Jean Louis Hébarre an Max Horkheimer, 1950-1952; 1 Brief mit Antwort von dem Hebedienst für Elektrizität, Gas und Wasser an Max Horkheimer, 1951; 5 Briefe mit Antwort und Beilage von Professor Otto Heckmann an Max Horkheimer, 1952, 1954; 1 Brief von Melvin J. Lasky an August Heckscher, 1957; 3 Briefe mit Antwort von Marie Heep an Max Horkheimer, 1956-1858; 1 Brief von der Buchhandlung Thekla Heer an Max Horkheimer, 1953; 1 Brief mit Antwort von dem Verleger Jakob Hegner an Max Horkheimer, 1955; 1 Brief von Dr. phil. Rudolf M. Heilbrunn an Max Horkheimer, 1953; 1 Brief mit Antwort von Professor Eduard Heimann an Max Horkheimer, 1952; 1 Brief von Professor Eduard Heimann an Theodor W. Adorno, 1957; 1 Brief mit Antwort von stud. phil. Wolfgang Heinrich an Max Horkheimer, 1958; 1 Brief von Max Horkheimer an den Direktor Helmuth Heintzmann, 1955; 1 Aktennotiz von Professor Bernhard Heller, 1956; 1 Brief mit Antwort von Philipp A. Heller an Max Horkheimer, 1952; 1 Brief von Max Horkheimer an Assistent Winfried Hellmann, 1957; 2 Briefe mit Antwort von Professor Arthur Henkel an Max Horkheimer, 1953/1954; 1 Brief von Max Horkheiemr an Dorothy Henkel, 1952; 2 Briefe mit Antwort von Dr. jur. Werner Hennig an Max Horkheimer, 1951; 1 Brief von Max Horkheimer an Professor Wilhelm Hennis, 1957; 3 Briefe mit Antwort und Beilage von Professor Fritz Hepner an Max Horkheimer, 1953; 1 Brief von Max Horkheimer an den Hessischer Minister für Erziehung und Volksbildung, 1950; 1 Brief mit Antwort von Professor Henrietta Herbolsheimer an Max Horkheimer, 1957/1958; 2 Briefe mit Antwort von P. G. Herbst an Max Horkheimer, 1952; 1 Brief von Max Horkheimer an den Herder Verlag, 1953; 2 Briefe mit Antwort, Beilagen und Aktennotizen von Guenter R. Herz an Max Horkheimer, 1956-1957; 2 Briefe mit Antwort unv Beilagen von Professor Theodor W. Adorno, von Dr. phil. Günther Herzberg an Max Horkheimer, 1951-1953; 1 Brief von Professor Theodor W. Adrono an Dr. phil. Günther Herzberg, 1951; 1 Brief von Dr. phil. G. Herzfeld an Max Horkheimer, 1952; 1 Brief von dem Herzog-Film an Max Horkheimer, 1952; 1 Brief mit Antwort von Professor Theodor W. Adorno, von Professor Erich Herzog an Max Horkheimer, 1952; 1 Brief von Professor Theodor W. Adorno an Professor Erich Herzog, 1952; 1 Brief mit Antwort von dem Verlag Otto H. Hess an Max Horkheimer, 1954; 1 Brief von Professor Gerhard Hess an Max Horkheimer, 1953; 1 Drucksachevon dem Hessischer Arbeitsausschuss gegen Rekrutierung, 1952; 1 Brief mit Beilage von dem Hotel Hessischer Hof an Max Horkheimer, 1956; 1 Brief mit Antwort von dem Hessischer Landesverband für Erwachsenenbildung an Max Horkheimer, 1956; 2 Briefe mit Antwort und Beilage von Marc Heurgon an Max Horkheimer, 1958; 1 Brief mit Beilage von Ruth Heydebrand an Max Horkheimer, [1955]; 1 Brief mit Antwort von Professor Frederick W. J. Heuser an Max Horkheimer, 1954; 2 Briefe mit Antwort von Professor Joh Erich Heyde an Max Horkheimer, 1958; 1 Befürwortung von Wolf von Heydebrand an Max Horkheimer, 1954; 1 Brief mit Antwort von Professor Heinz Joachim Heydorn an Max Horkheimer, 1953; 1 Brief mit Antwort und Beilage von dem Arzt Otto Heymann an Max Horkheimer, 1955; 5 Briefe zwischen dem Devisenberater und Steuerhelfer Joseph Christ und Max Horkheimer, 1955, 1956, 1961; 1 Brief von dem Office of the United States High Commissioner for Germany an Max Horkheimer, 1953; 1 Lebenslauf von Elen B. Hill, ohne Jahr; 1 Brief von Kurt H. Wolff an Max Horkheimer, 1952; 1 Brief von Rolf Himmelreich an Max Horkheimer, 1956; 1 Brief mit Antwort von Dr. Rolf Hinder an Max Horkheimer, 1953; 1 Brief mit Antwort von Anton Hinsinger an Max Horkheimer, 1953; 1 Brief mit Antwort von dem Hippokrates-Verlag an Max Horkheimer, 1952; 1 Brief von Bernice L. Hirsch anMax Horkheimer, 1957; 4 Briefe und Beilagen zwischen dem Historiker und Soziologe Helmut Hirsch an Max Horkheimer, 1951-1954, 25.05.1951; 3 Briefe mit Antwort von Lux Hirsch an Max Horkheimer, 1958; 1 Brief mit Antwort von Trude Hirschberg an Max Horkheimer, 1951; 1 Brief mit Antwort von Ingineur Paul F. Hirschfelder an Max Horkheimer, 1952; 1 Brief von Johannes Hirzel an Max Horkheimer, 1955; 1 Brief mit Antwort von dem Historisches Seminar Köln an Max Horkheimer, 1956; 1 Brief mit Antwort und Beilage von Professor Wolfgang Hochheimer an Professor Theodor W. Adorno, 1952; 2 Briefe von Max Horkheimer an Professor Wolfgang Hochheimer, 1953, 1954; 2 Memoranden von der Deutschen Gesellschaft für Psychologie, 1953; 1 Brief mit Beilage von Stud. phil. Erna Hochleitner an Max Horkheimer, 1956; 1 Brief mit Antwort von Professor Helmut Coing an Max Horkheimer, 1957; 3 Briefe mit Antwort von der Hochschule für Sozialwissenschaften Wilhelmshaven an Max Horkheimer, 1957, 1958; 1 Brief von Max Horkheimer an die Hochschule für Wirtschafts- und Sozialwissenschaften Nürnberg, 1953; 2 Drucksachen von dem Hochschul-Dienst, 1952; 2 Drucksachen von der Hochschule für politische Wissenschaften München, 1952; 1 Brief mit Antwort von Dr. Wolfram Hodermann an Max Horkheimer, 1951; 4 Briefe zwischen Dr. phil. Walter Höllerer und Max Horkheimer, 1956; 1 Brief mit Antwort von Privatdozent Dr. phil. Walter Hoeres anMax Horkheimer, 1956; 2 Briefe mit Antwort von Stud. phil. Charlotte Hoffmann an Max Horkheimer, 1950; 3 Briefe mit Antwort und Beilage von Professor Walter Hoffmann an Max Horkheimer, 1950-1955; 1 Brief mit Antwort von Wolfhart E. V. Hoffmann an Max Horkheimer, 1953; 1 Brief von Max Horkheimer an Dr. Werner Hofmann, 1956; 1 Glückwunschtelegramm mit Antwort von Ernst und Karl Hohner, 1953; 1 Brief von Dozent Uvo Hölscher an Max Horkheimer, 1950; 2 Briefe mit Antwort von Professor Dr. med. K. Holldack an Max Horkheimer, 1957; 2 Briefe mit Antwort von Dipl. Landwirt Bernhard Hollenhorst an Max Horkheimer, 1956; 1 Brief von Hans Heinz Holz an Max Horkheimer, 1951; 2 Briefe mit Antwort und Beilage von Dr. phil. Rudolf Holzinger an Max Horkheimer, 1951, 1952; 1 Brief mit Antwort von Jakob Hommen an Max Horkheimer, 1953; 1 Brief von Adele Hoppe anMax Horkheimer, 1953; 1 Brief mit Antwort von Dr. jur. Anton Horn an Max Horkheimer, 1954; 1 Brief mit Antwort von Dr. phil. Emil Horn an Max Horkheimer, 1953; 1 Brief von der Landesabgeordneten Ruth Horn an H. Maidon, 1953; 1 Brief mit Antwort von Reg.-Direktor Dr. phil. Kurt Horstmann an Max Horkheimer, 1953; 1 Brief von dem Hotel Baur au Lac an H. Maidon, 1958; 2 Briefe mit 1 Antwort von dem Hotel Frankfurter Hof an Max Horkheimer, 1956, 1958; 1 Brief mit Antwort von dem Hotel Stafflenberg an H. Maidon, 1953; 1 Brief von dem Hotel Vier Jahreszeiten, München an Max Horkheimer, 1951; 1 Brief von Max Horkheimer an Jean J. Hubener, 1951; 2 Briefe mit Antwort und Beilage von Susanna Huber-Weisser an Max Horkheimer, 1956; 1 Todesanzeige von dem Sozialgerichtsdirektor Gustav Adolf Hünniger, 1955; 1 Brief von dem Oberstudiendirektor F. Huf an Max Horkheimer, 1952; 1 Brief mit Antwort von Professor H. D. Huggins an Max Horkheimer, 1954; 2 Briefe mit 1 Antwort und 1 Beilage von dem Humboldt-Verlag, Wien-Stuttgart an Max Horkheimer, 1951; 1 Brief von Helge Pross an stud. rer. pol. Kristian Hungar, 1957; 1 Brief von Helmut Hungerland an Max Horkheimer, 1950; 1 Brief mit Antwort von James R. Huntley an Max Horkheimer, 1954; 1 Brief von Professor Robert Maynard Hutchins an Max Horkheimer, 1957;

(Table 1) GRACE-derived mass balance of the Greenland ice sheet 2002-2010

We re-evaluate the Greenland mass balance for the recent period using low-pass Independent Component Analysis (ICA) post-processing of the Level-2 GRACE data (2002-2010) from different official providers (UTCSR, JPL, GFZ) and confirm the present important ice mass loss in the range of -70 and -90 Gt/y of this ice sheet, due to negative contributions of the glaciers on the east coast. We highlight the high interannual variability of mass variations of the Greenland Ice Sheet (GrIS), especially the recent deceleration of ice loss in 2009-2010, once seasonal cycles are robustly removed by Seasonal Trend Loess (STL) decomposition. Interannual variability leads to varying trend estimates depending on the considered time span. Correction of post-glacial rebound effects on ice mass trend estimates represents no more than 8 Gt/y over the whole ice sheet. We also investigate possible climatic causes that can explain these ice mass interannual variations, as strong correlations between GRACE-based mass balance and atmosphere/ocean parallels are established: (1) changes in snow accumulation, and (2) the influence of inputs of warm ocean water that periodically accelerate the calving of glaciers in coastal regions and, feed-back effects of coastal water cooling by fresh currents from glaciers melting. These results suggest that the Greenland mass balance is driven by coastal sea surface temperature at time scales shorter than accumulation.