Bauen fürs Bürgertum: Der Kieler Architekt Johann Theede 1876-1934

Der Kieler Architekt Johann Theede (1876-1934) ist ein bedeutender Vertreter der Heimatschutzarchitektur in Schleswig-Holstein. Die Dissertation wertet einen zuvor nicht bekannten privaten Nachlass aus, der eine umfangreiche Darstellung zu Studium, Bildungsreisen und Frühwerk des Architekten erlaubt. Theedes Gesamtwerk wird in die deutsche und europäische Architektur zu Beginn des 20. Jahrhunderts eingeordnet

UNESCO als Label für Kieler Meeresforschung

Seit 1992 hat die UNESCO (United Nations Educational, Scientific and Cultural Organization) weltweit mehr als 600 Lehrstühle als »UNESCOLehrstuhl« ausgezeichnet. Zu den acht Lehrstuhlinhabern in Deutschland gehört Professor Wolf-Christian Dullo am GEOMAR Helmholtz-Zentrum für Ozeanforschung Kiel

Properties of non-structural protein 1 of Semliki Forest virus and its interference with virus replication

Semliki Forest virus (SFV) non-structural protein 1 (nsP1) is a major component of the virus replicase complex. It has previously been studied in cells infected with virus or using transient or stable expression systems. To extend these studies, tetracycline-inducible stable cell lines expressing SFV nsP1 or its palmitoylation-negative mutant (nsP16D) were constructed. The levels of protein expression and the subcellular localization of nsP1 in induced cells were similar to those in virus-infected cells. The nsP1 expressed by stable, inducible cell lines or by SFV-infected HEK293 T-REx cells was a stable protein with a half-life of approximately 5 h. In contrast to SFV infection, induction of nsP1 expression had no detectable effect on cellular transcription, translation or viability. Induction of expression of nsP1 or nsP16D interfered with multiplication of SFV, typically resulting in a 5–10-fold reduction in virus yields. This reduction was not due to a decrease in the number of infected cells, indicating that nsP1 expression does not block virus entry or initiation of replication. Expression of nsP1 interfered with virus genomic RNA synthesis and delayed accumulation of viral subgenomic RNA translation products. Expression of nsP1 with a mutation in the palmitoylation site reduced synthesis of genomic and subgenomic RNAs and their products of translation, and this effect did not resolve with time. These results are in agreement with data published previously, suggesting a role for nsP1 in genomic RNA synthesis

The rationale and design of TransCon Growth Hormone for the treatment of growth hormone deficiency

The fundamental challenge of developing a long-acting growth hormone (LAGH) is to create a more convenient growth hormone (GH) dosing profile while retaining the excellent safety, efficacy and tolerability of daily GH. With GH receptors on virtually all cells, replacement therapy should achieve the same tissue distribution and effects of daily (and endogenous) GH while maintaining levels of GH and resulting IGF-1 within the physiologic range. To date, only two LAGHs have gained the approval of either the Food and Drug Administration (FDA) or the European Medicines Agency (EMA); both released unmodified GH, thus presumably replicating distribution and pharmacological actions of daily GH. Other technologies have been applied to create LAGHs, including modifying GH (for example, protein enlargement or albumin binding) such that the resulting analogues possess a longer half-life. Based on these approaches, nearly 20 LAGHs have reached various stages of clinical development. Although most have failed, lessons learned have guided the development of a novel LAGH. TransCon GH is a LAGH prodrug in which GH is transiently bound to an inert methoxy polyethylene glycol (mPEG) carrier. It was designed to achieve the same safety, efficacy and tolerability as daily GH but with more convenient weekly dosing. In phase 2 trials of children and adults with growth hormone deficiency (GHD), similar safety, efficacy and tolerability to daily GH was shown as well as GH and IGF-1 levels within the physiologic range. These promising results support further development of TransCon GH

Vascular endothelial expression of indoleamine 2,3-dioxygenase 1 forms a positive gradient towards the feto-maternal interface.

We describe the distribution of indoleamine 2,3-dioxygenase 1 (IDO1) in vascular endothelium of human first-trimester and term placenta. Expression of IDO1 protein on the fetal side of the interface extended from almost exclusively sub-trophoblastic capillaries in first-trimester placenta to a nearly general presence on villous vascular endothelia at term, including also most bigger vessels such as villous arteries and veins of stem villi and vessels of the chorionic plate. Umbilical cord vessels were generally negative for IDO1 protein. In the fetal part of the placenta positivity for IDO1 was restricted to vascular endothelium, which did not co-express HLA-DR. This finding paralleled detectability of IDO1 mRNA in first trimester and term tissue and a high increase in the kynurenine to tryptophan ratio in chorionic villous tissue from first trimester to term placenta. Endothelial cells isolated from the chorionic plate of term placenta expressed IDO1 mRNA in contrast to endothelial cells originating from human umbilical vein, iliac vein or aorta. In first trimester decidua we found endothelium of arteries rather than veins expressing IDO1, which was complementory to expression of HLA-DR. An estimation of IDO activity on the basis of the ratio of kynurenine and tryptophan in blood taken from vessels of the chorionic plate of term placenta indicated far higher values than those found in the peripheral blood of adults. Thus, a gradient of vascular endothelial IDO1 expression is present at both sides of the feto-maternal interface

Paraffin sections of a uterine wall including the decidua in the 22^nd week of gestation, stained with anti-IDO1 antibody.

<p>The trophoblast-invaded implantation site shows strong staining of vascular endothelial cells (A). In the second quarter of the uterine wall most of the myometrial blood vessels are also labeled (B). The third quarter shows only one vessel stained (C) and in the outermost quarter of the uterus (D) none of the vessels stain for IDO1. Scale bar represents 200 µm.</p

Comparison of localization of IDO1 (A) and HLA-DR (B) in first trimester decidua.

<p>Serial paraffin sections are stained by immunohistochemistry. Designated are uterine glands (asterisks), the endothelium of spiral arteries (open arrowhead) and of veins (arrow). Please note that apart from expression in the endothelium of veins, HLA-DR is expressed by macrophages. Scale bar = 100 µm.</p

Illustration of the IDO1 expression gradient in vascular endothelial cells of fetal and maternal blood circulations at the utero-placental materno-fetal interface.

<p>The expression intensity increases close to the semi-allogeneic contact zone.</p