Stadtklimatologie im Wandel der Zeit – Einblicke aus Deutschland, Österreich und der Schweiz

Dieser Beitrag zeichnet die Entwicklung der wissenschaftlichen Beschäftigung mit dem Klima und der Luftqualität von Städten in kurzen, exemplarischen Zügen nach. Die Quellenlage lässt eine Analyse der etwa über 2000-jährigen Geschichte der Stadtklimaforschung zu. Es dürften wohl indische und römische Kulturen gewesen sein, die sich dem Problem der Überwärmung und insbesondere dem der Luftverschmutzung in ihren aufstrebenden städtischen Siedlungen zuerst annahmen. Zu Beginn dieses Artikels wird im Rahmen einer internationalen Gesamtschau ein kurzer Abriss dieses Teilgebiets der Umweltmeteorologie gegeben. Anschließend wird die lebhafte Geschichte der Stadtklimaforschung für Deutschland, Österreich und die Schweiz (Akronym: D-A-CH) an zahlreichen Beispielen und Meilensteinen der Entwicklung referiert.This article reviews the development of scientific research on climate and air quality in cities in short, exemplary sections. The literature allows for an analysis of the 2000-year history of urban climate research. Probably the Indian and Roman cultures were the first who addressed the problem of overheating and especially that of air pollution in their emerging urban settlements. At the beginning of this article, a brief outline of this branch of environmental meteorology is given as part of an overall international review. Subsequently, the lively history of urban climate research for Germany, Austria, and Switzerland (acronym: D-A-CH) will be reported using numerous examples and milestones of its development

Peptide Models - XXIV: An ab Initio Study on N-formyl-l-prolinamide With Trans Peptide Bond. The Existence or Non-existence of Alpha(l) And Epsilon(l) Conformations

N-formyl-L-prolinamide was subjected to geometry optimization at three levels of theory: HF/3-21G, HF/6-31G (d) and B3LYP/6-31G (d). At all three levels of computation the global minimum was gamma(L) (inverse gamma-Turn) backbone conformation with two ring-puckered forms "UP" and "DOWN". At HF/3-21G level of theory three backbone conformations were found gamma(L), epsilon(L), and alpha(L). At higher levels of theory the epsilon(L), and alpha(L) conformations disappeared. The ''UP'' and ''DOWN'' ring-puckered forms, in the gamma(L) backbone conformation, led to practically identical vibrational spectra at the B3LYP/6-31G (d) level of theory

Urban climate in central european cities and global climate change

Urban areas are among those most endangered with the potential global climate changes. The studies concerning the impact of global changes on local climate of cities are of a high significance for the urban inhabitants' health and wellbeing. This paper is the final report of a project (Urban climate in Central European cities and global climate change) with the aim to raise the public awareness on those issues in five Central European cities: Szeged (Hungary), Brno (Czech Republic), Bratislava (Slovakia), Kraków (Poland) and Vienna (Austria). Within the project, complex data concerning local geomorphological features, land use and long-term climatological data were used to perform the climate modelling analyses using the model MUKLIMO_3 provided by the German Weather Service (DWD)

Syndecan-1 and FGF-2, but Not FGF Receptor-1, Share a Common Transport Route and Co-Localize with Heparanase in the Nuclei of Mesenchymal Tumor Cells

Syndecan-1 forms complexes with growth factors and their cognate receptors in the cell membrane. We have previously reported a tubulin-mediated translocation of syndecan-1 to the nucleus. The transport route and functional significance of nuclear syndecan-1 is still incompletely understood. Here we investigate the sub-cellular distribution of syndecan-1, FGF-2, FGFR-1 and heparanase in malignant mesenchymal tumor cells, and explore the possibility of their coordinated translocation to the nucleus. To elucidate a structural requirement for this nuclear transport, we have transfected cells with a syndecan-1/EGFP construct or with a short truncated version containing only the tubulin binding RMKKK sequence. The sub-cellular distribution of the EGFP fusion proteins was monitored by fluorescence microscopy. Our data indicate that syndecan-1, FGF-2 and heparanase co-localize in the nucleus, whereas FGFR-1 is enriched mainly in the perinuclear area. Overexpression of syndecan-1 results in increased nuclear accumulation of FGF-2, demonstrating the functional importance of syndecan-1 for this nuclear transport. Interestingly, exogenously added FGF-2 does not follow the route taken by endogenous FGF-2. Furthermore, we prove that the RMKKK sequence of syndecan-1 is necessary and sufficient for nuclear translocation, acting as a nuclear localization signal, and the Arginine residue is vital for this localization. We conclude that syndecan-1 and FGF-2, but not FGFR-1 share a common transport route and co-localize with heparanase in the nucleus, and this transport is mediated by the RMKKK motif in syndecan-1. Our study opens a new perspective in the proteoglycan field and provides more evidence of nuclear interactions of syndecan-1

Remodeling of extracellular matrix by normal and tumor-associated fibroblasts promotes cervical cancer progression

Background: Comparison of tissue microarray results of 29 cervical cancer and 27 normal cervix tissue samples using immunohistochemistry revealed considerable reorganization of the fibrillar stroma of these tumors. Preliminary densitometry analysis of laminin-1, α -smooth muscle actin (SMA) and fibronectin immunostaining demonstrated 3.8-fold upregulation of laminin-1 and 5.2-fold increase of SMA in the interstitial stroma, indicating that these proteins and the activated fibroblasts play important role in the pathogenesis of cervical cancer. In the present work we investigated the role of normal and tumor-associated fibroblasts. Methods: In vitro models were used to throw light on the multifactorial process of tumor-stroma interaction, by means of studying the cooperation between tumor cells and fibroblasts. Fibroblasts from normal cervix and cervical cancers were grown either separately or in co-culture with CSCC7 cervical cancer cell line. Changes manifest in secreted glycoproteins, integrins and matrix metallo-proteases (MMPs) were explored. Results: While normal fibroblasts produced components of interstitial matrix and TGF- β 1 that promoted cell proliferation, cancer-associated fibroblasts (CAFs) synthesized ample amounts of laminin-1. The following results support the significance of laminin-1 in the invasion of CSCC7 cells: 1.) Tumor-associated fibroblasts produced more laminin-1 and less components of fibrillar ECM than normal cells; 2.) The production of laminin chains was further increased when CSCC7 cells were grown in co-culture with fibroblasts; 3.) CSCC7 cells were capable of increasing their laminin production; 4.) Tumor cells predominantly expressed integrin α 6 β 4 laminin receptors and migrated towards laminin. The integrin profile of both normal and tumor-associated fibroblasts was similar, expressing receptors for fibronectin, vitronectin and osteopontin. MMP-7 secreted by CSCC7 cells was upregulated by the presence of normal fibroblasts, whereas MMP-2 produced mainly by fibroblasts was activated in the presence of CSCC7 cells. Conclusions: Our results indicate that in addition to degradation of the basement membrane, invasion of cervical cancer is accomplished by the remodeling of the interstitial stroma, which process includes decrease and partial replacement of fibronectin and collagens by a laminin-rich matrix

Syndecan-1 Enhances Proliferation, Migration and Metastasis of HT-1080 Cells in Cooperation with Syndecan-2

Syndecans are transmembrane heparan sulphate proteoglycans. Their role in the development of the malignant phenotype is ambiguous and depends upon the particular type of cancer. Nevertheless, syndecans are promising targets in cancer therapy, and it is important to elucidate the mechanisms controlling their various cellular effects. According to earlier studies, both syndecan-1 and syndecan-2 promote malignancy of HT-1080 human fibrosarcoma cells, by increasing the proliferation rate and the metastatic potential and migratory ability, respectively. To better understand their tumour promoter role in this cell line, syndecan expression levels were modulated in HT-1080 cells and the growth rate, chemotaxis and invasion capacity were studied. For in vivo testing, syndecan-1 overexpressing cells were also inoculated into mice. Overexpression of full length or truncated syndecan-1 lacking the entire ectodomain but containing the four juxtamembrane amino acids promoted proliferation and chemotaxis. These effects were accompanied by a marked increase in syndecan-2 protein expression. The pro-migratory and pro-proliferative effects of truncated syndecan-1 were not observable when syndecan-2 was silenced. Antisense silencing of syndecan-2, but not that of syndecan-1, inhibited cell migration. In vivo, both full length and truncated syndecan-1 increased tumour growth and metastatic rate. Based on our in vitro results, we conclude that the tumour promoter role of syndecan-1 observed in HT-1080 cells is independent of its ectodomain; however, in vivo the presence of the ectodomain further increases tumour proliferation. The enhanced migratory ability induced by syndecan-1 overexpression is mediated by syndecan-2. Overexpression of syndecan-1 also leads to activation of IGF1R and increased expression of Ets-1. These changes were not evident when syndecan-2 was overexpressed. These findings suggest the involvement of IGF1R and Ets-1 in the induction of syndecan-2 synthesis and stimulation of proliferation by syndecan-1. This is the first report demonstrating that syndecan-1 enhances malignancy of a mesenchymal tumour cell line, via induction of syndecan-2 expression

Comprehensive DNA Methylation Analysis Reveals a Common Ten-Gene Methylation Signature in Colorectal Adenomas and Carcinomas

Microarray analysis of promoter hypermethylation provides insight into the role and extent of DNA methylation in the development of colorectal cancer (CRC) and may be co-monitored with the appearance of driver mutations. Colonic biopsy samples were obtained endoscopically from 10 normal, 23 adenoma (17 low-grade (LGD) and 6 high-grade dysplasia (HGD)), and 8 ulcerative colitis (UC) patients (4 active and 4 inactive). CRC samples were obtained from 24 patients (17 primary, 7 metastatic (MCRC)), 7 of them with synchronous LGD. Field effects were analyzed in tissues 1 cm (n = 5) and 10 cm (n = 5) from the margin of CRC. Tissue materials were studied for DNA methylation status using a 96 gene panel and for KRAS and BRAF mutations. Expression levels were assayed using whole genomic mRNA arrays. SFRP1 was further examined by immunohistochemistry. HT29 cells were treated with 5-aza-2' deoxycytidine to analyze the reversal possibility of DNA methylation. More than 85% of tumor samples showed hypermethylation in 10 genes (SFRP1, SST, BNC1, MAL, SLIT2, SFRP2, SLIT3, ALDH1A3, TMEFF2, WIF1), whereas the frequency of examined mutations were below 25%. These genes distinguished precancerous and cancerous lesions from inflamed and healthy tissue. The mRNA alterations that might be caused by systematic methylation could be partly reversed by demethylation treatment. Systematic changes in methylation patterns were observed early in CRC carcinogenesis, occuring in precursor lesions and CRC. Thus we conclude that DNA hypermethylation is an early and systematic event in colorectal carcinogenesis, and it could be potentially reversed by systematic demethylation therapy, but it would need more in vitro and in vivo experiments to support this theory

Über Peptidsynthesen, LVII Synthesen von Cyclopeptiden aus Glycin und zwei Paaren von Prolin

Um die Konformation, das Komplexbildungsvermögen mit Natriumionen und die vor Phallotoxinen schützende Wirkung von Cyclopeptiden zu studieren, die – wie das natürliche Antitoxin Antamanid – 2 Paare von Prolinresten enthalten, wurden die vereinfachten, außer Prolin nur Glycin enthaltenden Cyclopeptide 2a–e mit 6–10 Aminosäureresten synthetisiert