The intercellular binding of desmosomal junctions is mediated by cadherins of the desmoglein (Dsg) and desmocollin (Dsc) type. Dsg2 mutant mice with deletion of a substantial segment of the ...extracellular EC1-EC2 domain, which is believed to participate in homo- and heterophilic desmosomal cadherin interactions, develop cardiac fibrosis and ventricular dilation. Widening of the intercellular cleft and complete intercalated disc ruptures can be observed in the hearts of these mice. Since a reduced litter size of homozygous Dsg2 mutant mice was noted and a functional correlation between desmosomes and embryo implantation has been deduced from animal studies, we looked for an alteration of desmosomes in uterine endometrial epithelium. Shape and number of desmosomes as well as the expression of Dsg2 and the desmosomal plaque protein desmoplakin (Dsp) were investigated by electron microscopy and immunohistochemistry in 12 oestrous-dated mice (7 wild type and 5 homozygous Dsg2 mutant mice) at the age of 9–17 weeks. The immunohistochemical detection of Dsg2 was diminished in the mutants and the number of desmosomes was significantly reduced as revealed by electron microscopy. In addition, the intercellular desmosomal space measured in electron micrographs was considerably widened in the Dsg2 mutants. The increased intercellular spacing can be explained by the partial deletion of the extracellular EC1–EC2 domain of Dsg2. Whether these changes explain the reduced number of offspring of homozygous Dsg2 mutant mice remains to be further investigated.
Quinoidal Azaacenes: 99 % Diradical Character Intorp, Sebastian N.; Hodecker, Manuel; Müller, Matthias ...
Angewandte Chemie (International ed.),
July 20, 2020, Letnik:
59, Številka:
30
Journal Article
Recenzirano
Odprti dostop
Quinoidal azaacenes with almost pure diradical character (y=0.95 to y=0.99) were synthesized. All compounds exhibit paramagnetic behavior investigated by EPR and NMR spectroscopy, and SQUID ...measurements, revealing thermally populated triplet states with an extremely low‐energy gap ΔEST′ of 0.58 to 1.0 kcal mol−1. The species are persistent in solution (half‐life≈14–21 h) and in the solid state they are stable for weeks.
Best of two worlds: Lateral fusion of azaacenes onto a quinoidal system furnishes stable diradicals with a radical character (y) of up to 0.99. All compounds exhibit paramagnetic behavior as determined by EPR and NMR spectroscopy and SQUID measurements, revealing thermally populated triplet states with an extremely low‐energy gap ΔEST of 0.58 to 1.0 kcal mol−1. The species are persistent in solution (half‐life≈14–21 h), and they are stable for weeks in the solid state.
A hypoxic microenvironment induces resistance to alkylating agents by activating targets in the mammalian target of rapamycin (mTOR) pathway. The molecular mechanisms involved in this mTOR-mediated ...hypoxia-induced chemoresistance, however, are unclear. Here we identify the mTOR target N -myc downstream regulated gene 1 (NDRG1) as a key determinant of resistance toward alkylating chemotherapy, driven by hypoxia but also by therapeutic measures such as irradiation, corticosteroids, and chronic exposure to alkylating agents via distinct molecular routes involving hypoxia-inducible factor (HIF)-1alpha, p53, and the mTOR complex 2 (mTORC2)/serum glucocorticoid-induced protein kinase 1 (SGK1) pathway. Resistance toward alkylating chemotherapy but not radiotherapy was dependent on NDRG1 expression and activity. In posttreatment tumor tissue of patients with malignant gliomas, NDRG1 was induced and predictive of poor response to alkylating chemotherapy. On a molecular level, NDRG1 bound and stabilized methyltransferases, chiefly O ⁶-methylguanine-DNA methyltransferase (MGMT), a key enzyme for resistance to alkylating agents in glioblastoma patients. In patients with glioblastoma, MGMT promoter methylation in tumor tissue was not more predictive for response to alkylating chemotherapy in patients who received concomitant corticosteroids.
Puzzling over a diradicalPiecing together the “correct” combination of an azaacene, phenoxyl groups, and dithienobenzene regioisomers has been rewarded by the generation of quinoidal azaacenes with ...almost pure diradical character that are stable for weeks in the solid state and persistent in solution, as described by J. Freudenberg, U. H. F. Bunz and co‐workers in their Communication on page 12396.
Quinoidal Azaacenes: 99 % Diradical Character Intorp, Sebastian N.; Hodecker, Manuel; Müller, Matthias ...
Angewandte Chemie,
July 20, 2020, Letnik:
132, Številka:
30
Journal Article
Recenzirano
Odprti dostop
Quinoidal azaacenes with almost pure diradical character (y=0.95 to y=0.99) were synthesized. All compounds exhibit paramagnetic behavior investigated by EPR and NMR spectroscopy, and SQUID ...measurements, revealing thermally populated triplet states with an extremely low‐energy gap ΔEST′ of 0.58 to 1.0 kcal mol−1. The species are persistent in solution (half‐life≈14–21 h) and in the solid state they are stable for weeks.
Best of two worlds: Lateral fusion of azaacenes onto a quinoidal system furnishes stable diradicals with a radical character (y) of up to 0.99. All compounds exhibit paramagnetic behavior as determined by EPR and NMR spectroscopy and SQUID measurements, revealing thermally populated triplet states with an extremely low‐energy gap ΔEST of 0.58 to 1.0 kcal mol−1. The species are persistent in solution (half‐life≈14–21 h), and they are stable for weeks in the solid state.
Diradikal‐Puzzle Der Zusammenbau der richtigen Kombination aus einem Azaacen, Phenoxylgruppen und Dithienobenzol‐Regioisomeren wird mit chinoidalen Azacenen mit nahezu reinem Diradikalcharakter ...belohnt, die im festen Zustand über Wochen stabil und auch in Lösung haltbar sind. Mehr Informationen finden sich in der Zuschrift von J. Freudenberg, U. H. F. Bunz et al. auf S. 12496.
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