Intraligand Charge Transfer Enables Visible‐Light‐Mediated Nickel‐Catalyzed Cross‐Coupling Reactions

We demonstrate that several visible‐light‐mediated carbon−heteroatom cross‐coupling reactions can be carried out using a photoactive NiII precatalyst that forms in situ from a nickel salt and a bipyridine ligand decorated with two carbazole groups (Ni(Czbpy)Cl2). The activation of this precatalyst towards cross‐coupling reactions follows a hitherto undisclosed mechanism that is different from previously reported light‐responsive nickel complexes that undergo metal‐to‐ligand charge transfer. Theoretical and spectroscopic investigations revealed that irradiation of Ni(Czbpy)Cl2 with visible light causes an initial intraligand charge transfer event that triggers productive catalysis. Ligand polymerization affords a porous, recyclable organic polymer for heterogeneous nickel catalysis of cross‐coupling reactions. The heterogeneous catalyst shows stable performance in a packed‐bed flow reactor during a week of continuous operation

Histological assessment of paxgene tissue fixation and stabilization reagents

Within SPIDIA, an EC FP7 project aimed to improve pre analytic procedures, the PAXgene Tissue System (PAXgene), was designed to improve tissue quality for parallel molecular and morphological analysis. Within the SPIDIA project promising results were found in both genomic and proteomic experiments with PAXgene-fixed and paraffin embedded tissue derived biomolecules. But, for this technology to be accepted for use in both clinical and basic research, it is essential that its adequacy for preserving morphology and antigenicity is validated relative to formalin fixation. It is our aim to assess the suitability of PAXgene tissue fixation for (immuno)histological methods. Normal human tissue specimens (n = 70) were collected and divided into equal parts for fixation either with formalin or PAXgene. Sections of the obtained paraffin-embedded tissue were cut and stained. Morphological aspects of PAXgene-fixed tissue were described and also scored relative to formalin-fixed tissue. Performance of PAXgene-fixed tissue in immunohistochemical and in situ hybridization assays was also assessed relative to the corresponding formalin-fixed tissues. Morphology of PAXgene-fixed paraffin embedded tissue was well preserved and deemed adequate for diagnostics in most cases. Some antigens in PAXgene-fixed and paraffin embedded sections were detectable without the need for antigen retrieval, while others were detected using standard, formalin fixation based, immunohistochemistry protocols. Comparable results were obtained with in situ hybridization and histochemical stains. Basically all assessed histological techniques were found to be applicable to PAXgene-fixed and paraffin embedded tissue. In general results obtained with PAXgene-fixed tissue are comparable to those of formalin-fixed tissue. Compromises made in morphology can be called minor compared to the advantages in the molecular pathology possibilities

Machi: Neighborhood and Small Town—The Foundation for Urban Transformation in Japan

The term machi, signifying both neighborhood and small town, is a key element for understanding Japanese urban form and city planning. After tracing the origins of the term, this article explores the historic and contemporary significance of the concept and its particular spatial and socioeconomic forms. The article then argues that the concept of machi influenced the ways in which Japanese planners picked up foreign concepts through the nineteenth and particularly the twentieth century, absorbing some ideas and rejecting others. Building on their perception of the city as composed of urban units that allowed for planning in patchwork patterns, leading Japanese planners carefully selected models—independently of international appreciation—making, for example, the book The New Town by the German planner Gottfried Feder a standard reference. The article concludes by arguing that foreign observers must understand the concept of machi to comprehend contemporary Japanese neighborhoods, city life, and urban forms

Lgl2 Executes Its Function as a Tumor Suppressor by Regulating ErbB Signaling in the Zebrafish Epidermis

Changes in tissue homeostasis, acquisition of invasive cell characteristics, and tumor formation can often be linked to the loss of epithelial cell polarity. In carcinogenesis, the grade of neoplasia correlates with impaired cell polarity. In Drosophila, lethal giant larvae (lgl), discs large (dlg), and scribble, which are components of the epithelial apico-basal cell polarity machinery, act as tumor suppressors, and orthologs of this evolutionary conserved pathway are lost in human carcinoma with high frequency. However, a mechanistic link between neoplasia and vertebrate orthologs of these tumor-suppressor genes remains to be fully explored at the organismal level. Here, we show that the pen/lgl2 mutant phenotype shares two key cellular and molecular features of mammalian malignancy: cell autonomous epidermal neoplasia and epithelial-to-mesenchymal-transition (EMT) of basal epidermal cells including the differential expression of several regulators of EMT. Further, we found that epidermal neoplasia and EMT in pen/lgl2 mutant epidermal cells is promoted by ErbB signalling, a pathway of high significance in human carcinomas. Intriguingly, EMT in the pen/lgl2 mutant is facilitated specifically by ErbB2 mediated E-cadherin mislocalization and not via canonical snail–dependent down-regulation of E-cadherin expression. Our data reveal that pen/lgl2 functions as a tumor suppressor gene in vertebrates, establishing zebrafish pen/lgl2 mutants as a valuable cancer model