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One-chip integrated dual amperometric/field-effect sensor for the detection of dissolved hydrogen
(2011)
The anticancer activity of titanium complexes has been known since the groundbreaking studies of Köpf and Köpf-Maier on titanocen dichloride. Unfortunately, possibly due to their fast hydrolysis, derivatives of titanocen dichloride failed in clinical studies. Recently, the new family of titanium salan complexes containing tetradentate ONNO ligands with anti-cancer properties has been discovered. These salan complexes are much more stabile in aqueous media. In this study we describe the biological activity of two titanium salan complexes in a mouse model of cervical cancer. High efficiency of this promising complex family was demonstrated for the first time in vivo. From these data we conclude that titanium salan complexes display very strong antitumor properties exhibiting only minor side effects. Our results may influence the chemotherapy with metallo therapeutics in the future.
Meiotic functions of RAD18
(2011)
Inagaki, Akiko ; Sleddens-Linkels, Esther ; Wassenaar, Evelyne ; Ooms, Marja ; Cappellen, Wiggert A. van ; Hoeijmakers, Jan H. J. ; Seibler, Jost ; Vogt, Thomas F. ; Shin, Myung K. ; Grootegoed, J. Anton ; Baarends, Willy M.
Jordan, Sabine D. ; Krüger, Markus ; Willmes, Diana M. ; Redemann, Nora ; Wunderlich, F. Thomas ; Brönneke, Hella S. ; Merkwirth, Carsten ; Kashkar, Hamid ; Olkkonen, Vesa M. ; Böttger, Thomas ; Braun, Thomas ; Seibler, Jost ; Brüning, Jens C.
The contribution of altered post-transcriptional gene silencing to the development of insulin resistance and type 2 diabetes mellitus so far remains elusive. Here, we demonstrate that expression of microRNA (miR)-143 and 145 is upregulated in the liver of genetic and dietary mouse models of obesity. Induced transgenic overexpression of miR-143, but not miR-145, impairs insulin-stimulated AKT activation and glucose homeostasis. Conversely, mice deficient for the miR-143–145 cluster are protected from the development of obesity-associated insulin resistance. Quantitative-mass-spectrometry-based analysis of hepatic protein expression in miR-143-overexpressing mice revealed miR-143-dependent downregulation of oxysterol-binding-protein-related protein (ORP) 8. Reduced ORP8 expression in cultured liver cells impairs the ability of insulin to induce AKT activation, revealing an ORP8-dependent mechanism of AKT regulation. Our experiments provide direct evidence that dysregulated post-transcriptional gene silencing contributes to the development of obesity-induced insulin resistance, and characterize the miR-143–ORP8 pathway as a potential target for the treatment of obesity-associated diabetes.