Activation of extracellular signal-regulated kinase in proliferative glomerulonephritis in rats

Multiple extracellular mitogens are involved in the pathogenesis of proliferative forms of glomerulonephritis (GN), In vitro studies demonstrate the pivotal role of extracellular signal-regulated kinase (ERK) in the regulation of cellular proliferation in response to extracellular mitogens. In this study, we examined whether this kinase, as a convergence point of mitogenic stimuli, is activated in proliferative GN in vivo, Two different proliferative forms of anti-glomerular basal membrane (GEM) GN in rats were induced and whole cortical tissue as well as isolated glomeruli examined using kinase activity assays and Western blot analysis, Administration of rabbit anti-rat GEM serum to rats, preimmunized with rabbit IgG, induced an accelerated crescentic anti-GEM GN. A significant increase in cortical, and more dramatically glomerular ERK activity was detected at 1, 3, and 7 d after induction of GN, Immunization of Wistar-Kyoto rats with bovine GEM also induced a crescentic anti-GBM GN with an increase of renal cortical ERK activity after 4, 6, and 8 wk, ERK is phosphorylated and activated by the MAP kinase/ERK kinase (MEK), We detected a significant increase in the expression of glomerular MEK in the accelerated form of anti-GEM CN, providing a possible mechanism of long-term activation of ERK in this disease model, In contrast to ERK, activation of stress-activated protein kinase was only detectable at early stages of proliferative GN, indicating these related kinases to serve distinct roles in the pathogenesis of GN, Our observations point to ERK as a putative mediator of the proliferative response to immune injury in GN and suggest that upregulation of MEK is involved in the long-term regulation of ERK in vivo.

Chemically engineering ligand selectivity at the free fatty acid receptor 2 based on pharmacological variation between species orthologs

When it is difficult to develop selective ligands within a family of related G-protein-coupled receptors (GPCRs), chemically engineered receptors activated solely by synthetic ligands (RASSLs) are useful alternatives for probing receptor function. In the present work, we explored whether a RASSL of the free fatty acid receptor 2 (FFA2) could be developed on the basis of pharmacological variation between species orthologs. For this, bovine FFA2 was characterized, revealing distinct ligand selectivity compared with human FFA2. Homology modeling and mutational analysis demonstrated a single mutation in human FFA2 of C4.57G resulted in a human FFA2 receptor with ligand selectivity similar to the bovine receptor. This was exploited to generate human FFA2-RASSL by the addition of a second mutation at a known orthosteric ligand interaction site, H6.55Q. The resulting FFA2-RASSL displayed a >100-fold loss of activity to endogenous ligands, while responding to the distinct ligand sorbic acid with pEC(50) values for inhibition of cAMP, 5.83 ± 0.11; Ca(2+) mobilization, 4.63 ± 0.05; ERK phosphorylation, 5.61 ± 0.06; and dynamic mass redistribution, 5.35 ± 0.06. This FFA2-RASSL will be useful in future studies on this receptor and demonstrates that exploitation of pharmacological variation between species orthologs is a powerful method to generate novel chemically engineered GPCRs.-Hudson, B. D., Christiansen, E., Tikhonova, I. G., Grundmann, M., Kostenis, E., Adams, D. R., Ulven, T., Milligan, G. Chemically engineering ligand selectivity at the free fatty acid receptor 2 based on pharmacological variation between species orthologs.

Design and Practice in Architectural Theory Education

Benefiting from design in theory learning is not common in architecture schools. The general practice is to design in studio and to theorise in lectures. In the undergraduate module History and Theory in Architecture II at Queen’s University Belfast, students attend interactive lectures, participate in reading group discussions, design TextObjects, and write essays. TextObjects contain textual, audio and/or graphic representations that highlight a single concept or a complex set of issues derived from readings. Students experiment with diverse media, such as filmmaking, photography, and graphic design, some of which they experience for the first time. Lectures and readings revolve around theories of architectural representation, media and communication, which are practiced through TextObjects. This is a new way to link theory and practice in architectural education. Through action research, this study analyses this innovative teaching method called TextObject, which brings design and practice into architectural theory education to stimulate students towards critical thinking. The pedagogical research of architectural theoretician Necdet Teymur (1992, 1996, 2002) underlies the study.

MAP kinase pathway signalling is essential for extracellular matrix determined mammary epithelial cell survival

Mammary epithelial cells in primary cell culture require both growth factors and specific extracellular matrix (ECM)-attachment for survival. Here we demonstrate for the first time that inhibition of the ECM-induced Erk 1/Erk 2 (p42/44 MAPK) pathway, by PD 98059, leads to apoptosis in these cells. Associated with this cell death is a possible compensatory signalling through the p38 MAP kinase pathway the inhibition of which, by SB 203580, leads to a more rapid onset of apoptosis. This provides evidence for a hitherto undescribed Erk 1/Erk 2 to p38 MAP kinase pathway 'cross-talk' that is essential for the survival of these cells. The cell death associated with inhibition of these two MAP kinase pathways however, occurred in the presence of insulin that activates the classical PI-3 kinase-dependent Akt/PKB survival signals and Akt phosphorylation. Cell death induced by inhibition of the MAP kinase pathways did not affect Akt phosphorylation and may, thus, be independent of PI-3 kinase signalling.

Changing Paradigms in Space Theories:Recapturing 20th Century Architectural History

The concept of space entered architectural history as late as 1893. Studies in art opened up the discussion, and it has been studied in various ways in architecture ever since. This article aims to instigate an additional reading to architectural history, one that is not supported by "isms" but based on space theories in the 20th century. Objectives of the article are to bring the concept of space and its changing paradigms to the attention of architectural researchers, to introduce a conceptual framework to classify and clarify theories of space, and to enrich the discussions on the 20th century architecture through theories that are beyond styles. The introduction of space in architecture will revolve around subject-object relationships, three-dimensionality and senses. Modern space will be discussed through concepts such as empathy, perception, abstraction, and geometry. A scientific approach will follow to study the concept of place through environment, event, behavior, and design methods. Finally, the research will look at contemporary approaches related to digitally supported space via concepts like reality-virtuality, mediated experience, and relationship with machines.

Cinematic and Architectonic Space in Tarkovsky's Solaris

Architecture plays an important role in Andrei Tarkovsky’s films in defining the atmosphere of a space and memory of a place. This paper is a study of how the settings in Tarkovsky’s Solaris (1972) are used to provoke and convey feelings to the audience through architectonic space depicting the city, library, home and aspects of the home such as paintings and mirrors. The rooms depicted in Solaris (Fig. 1) are filled with symbolism and detail. They are imbued with a poetic quality rarely seen in cinema. The everyday places of city, library and home in Solaris are given an emotional depth not usually found in these spaces in reality. Solaris is an anomaly among Tarkovsky’s films in that the majority of the narrative takes place in an enclosed built set. Rarely do Tarkovsky spaces exert so much control over the actors’ movements within a meticulously designed and detailed set. This paper analyses how the director uses constructed sets in Solaris to confront our perception of memories, dreams and reality.
The intent of this study is to gain better understanding of the link between architecture and other art forms such as painting and cinema through spatial analysis. This study also relates to our imagination and how we perceive architectonic space portrayed through cinematic images. The architectural theory of Juhani Pallasmaa forms the basis of this paper.

Sinemada Mimarlik

This is a special 'Architecture and Cinema' dossier edited for Arredamento, with several articles by different authors. Each article analyses spaces and cities represented in one particular feature film. The introductory essay is also by the dossier editor.

The Making of Modern Turkish Architecture

This is the introductory essay of ARCAM’s (Architectuurcentrum Amsterdam) “Turkey Today: Contemporary Turkish Architecture in Turkey and the Netherlands” Exhibit, which took place in September-November 2004 in Amsterdam, The Netherlands. The author also consulted the curators.

Odile Decq'i Anlamak

This is an interview with the well-known French architect Odile Decq.

ARCAM Sergisi:Modern Turkiyeyi Anlamak

This is an interview with the author about the "Turkey Today: Contemporary Turkish Architecture in Turkey and the Netherlands” Exhibition in Amsterdam, The Netherlands. The author consulted the curators and wrote the introductory essay of the exhibition.