Functional characterisation of the maturation of the blood-brain barrier in larval zebrafish.

Zebrafish are becoming increasingly popular as an organism in which to model human disease and to study the effects of small molecules on complex physiological and pathological processes. Since larvae are no more than a few millimetres in length, and can live in volumes as small as 100 microliters, they are particularly amenable to high-throughput and high content compound screening in 96 well plate format. There is a growing literature providing evidence that many compounds show similar pharmacological effects in zebrafish as they do in mammals, and in particular humans. However, a major question regarding their utility for small molecule screening for neurological conditions is whether a molecule will reach its target site within the central nervous system. Studies have shown that Claudin-5 and ZO-1, tight-junction proteins which are essential for blood-brain barrier (BBB) integrity in mammals, can be detected in some cerebral vessels in zebrafish from 3 days post-fertilisation (d.p.f.) onwards and this timing coincides with the retention of dyes, immunoreactive tracers and fluorescent markers within some but not all cerebral vessels. Whilst these findings demonstrate that features of a BBB are first present at 3 d.p.f., it is not clear how quickly the zebrafish BBB matures or how closely the barrier resembles that of mammals. Here, we have combined anatomical analysis by transmission electron microscopy, functional investigation using fluorescent markers and compound uptake using liquid chromatography/tandem mass spectrometry to demonstrate that maturation of the zebrafish BBB occurs between 3 d.p.f. and 10 d.p.f. and that this barrier shares both structural and functional similarities with that of mammals

Germany must invest more in its future

Shortly before the parliamentary election in 2013, Germany is riding on a wave of euphoria: hardly any other euro country has weathered the financial and debt crisis so well. Since 2009, GDP has grown by over eight percent and 1.2 million new jobs have been created. Public finances were consolidated and, in 2012, there was a fiscal surplus of 0.2 percent of GDP. An impressive financial position indeed for a country that, only ten years ago, was considered the sick man of Europe. But it is also a deceptive one. If one substitutes these for other comparative figures, then this image is seriously tarnished. Since 1999, Germany has achieved lower economic growth than the rest of the euro area. Real wages have barely increased since 1999 and real consumer spending has grown much more in the euro area on average than in Germany. In addition, German net public assets have contracted significantly. In 1999, net state assets were about 20 percent of GDP and, by 2011, they had declined to 0.5 percent of GDP and are, therefore, no longer available for future generations. In many areas, Germany has not really progressed at all and in some areas it has fallen significantly behind other countries. These arrears have not been balanced out by recent positive developments

Deutschland muss mehr in seine Zukunft investieren

Kurz vor der Bundestagswahl 2013 schwimmt Deutschland in den Augen der Ökonomen auf einer Welle der Euphorie: Kaum ein anderes Euroland hat die Finanz- und Schuldenkrise so gut gemeistert. Das deutsche Bruttoinlandsprodukt ist seit 2009 um mehr als acht Prozent gewachsen, es entstanden rund 1,2 Millionen neue Arbeitsplätze. Die öffentlichen Haushalte wurden konsolidiert, im Jahr 2012 gab es einen fiskalischen Überschuss von 0,2 Prozent des Bruttoinlandsprodukts. Eine glänzende Bilanz für ein Land, das vor zehn Jahren noch als der kranke Mann Europas galt - aber auch eine einseitige. Setzt man andere Vergleichsgrößen an, trübt sich das Bild erheblich ein: Seit 1999 hat Deutschland im Vergleich zum Euroraum ein niedrigeres Wirtschaftswachstum erzielt. Die Reallöhne sind seit 1999 kaum gestiegen, und die realen Konsumausgaben haben im Eurozonen-Durchschnitt deutlich kräftiger zugenommen als in Deutschland. Stark geschrumpft ist das deutsche Staatsvermögen: Lag es 1999 noch bei etwa 20 Prozent des Bruttoinlandsprodukts, so ist es bis 2011 auf 0,5 Prozent des Bruttoinlandsprodukts zusammengeschmolzen und steht damit für künftige Generationen nicht mehr zur Verfügung. In vielen Bereichen ist Deutschland nicht wirklich vorangekommen, in einigen deutlich hinter andere Länder zurückgefallen. Diese Rückstände sind durch die zuletzt gute Entwicklung nicht wieder aufgeholt worden

Digitalisierung beruflicher Lern- und Arbeitsprozesse. Impulse aus der Bauwirtschaft und anderen gewerblich-technischen Sektoren

Der Sammelband stellt aktuelle Ansätze zum digital unterstützten beruflichen Lernen dar. Die Beiträge geben Einblicke in die dynamische Entwicklung der Schnittstellen von Erwerbsarbeit und beruflicher Aus-, Fort- und Weiterbildung im Kontext der Digitalisierung Arbeits- und Lernmitteln. Der Band schließt damit an die 2019 ebenfalls im Universitätsverlag der Technischen Universität Berlin erschienene Publikation „Berufsbildung am Bau digital“ (hrsg. von Bernd Mahrin und Johannes Meyser) an. Das erste Kapitel erörtert grundsätzliche didaktische Fragen zu digital unterstütztem Lernen und Arbeiten einschließlich der Rahmenbedingungen. Im zweiten Kapitel schließen sich Beiträge zur Kapazitätsentwicklung, zu Standards und zu digitalen Werkzeugen an. Das dritte Kapitel widmet sich konkreten Einzellösungen mit starkem Praxisbezug und hohem Transferpotenzial zum digitalisierten Arbeiten und Lernen im Bausektor und im Metallbereich. Das abschließende vierte Kapitel präsentiert übergreifend nutzbare und frei zugängliche Online-Angebote wie einen Medienpool für Bildungszwecke, eine Lernmedien-Datenbank und ein hybrides Lernsystem mit virtuellem 3D-Gebäudemodell. Das Buch ist entstanden im Rahmen des durch das Bundesministerium für Bildung und Forschung und den Europäischen Sozialfonds geförderten Projektes DigiBAU – Digitales Bauberufliches Lernen und Arbeiten. (DIPF/Orig.)The anthology presents current approaches to digitally supported professional learning. The articles provide insights into the dynamic development of the interfaces between gainful employment and vocational training and further education in the context of digitization of work and learning aids. The volume is thus connected to the publication “Berufsbildung am Bau digital” (edited by Bernd Mahrin and Johannes Meyser), which was published in 2019 by the University Press of the Technische Universität Berlin. The first chapter discusses fundamental didactic questions about digitally supported learning and working, including the framework conditions. The second chapter picks contributions on capacity development, standards, and digital tools out as central themes. The third chapter is dedicated to concrete specific solutions with strong practical relevance and high transfer potential for digitized work and learning in the construction sector and in the metal sector. The final fourth chapter presents comprehensive and freely accessible online offers such as a media pool for educational purposes, a learning media database and a hybrid learning system with a virtual 3D building model. The book was created as part of the DigiBAU project - digital vocational learning and working in the field of construction - funded by the German Federal Ministry of Education and Research and the European Social Fund. (DIPF/Orig.

The Prospects of the Baby Boomers: Methodological Challenges in Projecting the Lives of an Aging Cohort

In most industrialized countries, the work and family patterns of the baby boomers characterized by more heterogeneous working careers and less stable family lives set them apart from preceding cohorts. Thus, it is of crucial importance to understand how these different work and family lives are linked to the boomers' prospective material well-being as they retire. This paper presents a new and unique matching-based approach for the projection of the life courses of German baby boomers, called the LAW-Life Projection Model. Basis for the projection are data from 27 waves of the German Socio-Economic Panel linked with administrative pension records from the German Statutory Pension In-surance that cover lifecycle pension-relevant earnings. Unlike model-based micro simula-tions that age the data year by year our matching-based projection uses sequences from older birth cohorts to complete the life-courses of statistically similar baby boomers through to retirement. An advantage of this approach is to coherently project the work-life and family trajectories as well as lifecycle earnings. The authors present a benchmark anal-ysis to assess the validity and accuracy of the projection. For this purpose, they cut a signif-icant portion of already lived lives and test different combinations of matching algorithms and donor pool specifications to identify the combination that produces the best fit be-tween previously cut but observed and projected life-course information. Exploiting the advantages of the projected data, the authors compare the returns to education - measured in terms of pension entitlements - across cohorts. The results indicate that within cohorts, differences between individuals with low and high educational attainment increase over time for men and women in East and West Germany. East German boomer women with low educational attainment face the most substantial losses in pension entitlements that put them at a high risk of being poor as they retire

Zebrafish Neurolin-a and -b, Orthologs of ALCAM, are Involved in Retinal Ganglion Cell Differentiation and Retinal Axon Pathfinding

Neurolin-a and Neurolin-b (also called alcam and nlcam, respectively) are zebrafish orthologs of human ALCAM, an adhesion protein of the immunoglobulin superfamily with functions in axon growth and guidance. Within the developing zebrafish retina, onset and progression of Neurolin-a expression parallels the pattern of retinal ganglion cell (RGC) differentiation. By using a morpholino-based knockdown approach, we show that Neurolin-a (but not Neurolin-b) is necessary for a crucial step in RGC differentiation. Without Neurolin-a, a large proportion of RGCs fail to develop, and RGC axons are absent or reduced in number. Subsequently, Neurolin-a is required for RGC survival and for the differentiation of all other retinal neurons. Neurolin-b is expressed later in well-differentiated RGCs and is required for RGC axon pathfinding. Without Neurolin-b, RGC axons grow in highly aberrant routes along the optic tract and/or fail to reach the optic tectum. Thus, the zebrafish Neurolin paralogs are involved in distinct steps of retinotectal development