Hemoglobin causes both endothelium-dependent and endothelium-independent contraction of the pig coronary arteries, independently of an inhibition of EDRF effects

Hemoglobin is widely used as an inhibitor of EDRF effects. Hemoglobin contracts pig coronary arteries in vitro. However, during this contraction, effects of substance P and bradykinin which act via the EDRF are not inhibited. This means that the hemoglobin contraction is not caused by inhibition of the EDRF. This contraction is caused by a substance released from the endothelium, and by eicosano?ds released from the smooth muscles.     

HNPCC-like cancer predisposition in mice through simultaneous loss of Msh3 and Msh6 mismatch-repair protein functions.

Cancer predisposition in hereditary non-polyposis colon cancer (HNPCC) is caused by defects in DNA mismatch repair (MMR). Mismatch recognition is attributed to two heterodimeric protein complexes: MutSalpha (refs 2, 3, 4, 5), a dimer of MutS homologues MSH2 and MSH6; and MutSbeta (refs 2,7), a dimer of MSH2 and MSH3. These complexes have specific and redundant mismatch recognition capacity. Whereas MSH2 deficiency ablates the activity of both dimers, causing strong cancer predisposition in mice and men, loss of MSH3 or MSH6 (also known as GTBP) function causes a partial MMR defect. This may explain the rarity of MSH6 and absence of MSH3 germline mutations in HNPCC families. To test this, we have inactivated the mouse genes Msh3 (formerly Rep3 ) and Msh6 (formerly Gtmbp). Msh6-deficient mice were prone to cancer; most animals developed lymphomas or epithelial tumours originating from the skin and uterus but only rarely from the intestine. Msh3 deficiency did not cause cancer predisposition, but in an Msh6 -deficient background, loss of Msh3 accelerated intestinal tumorigenesis. Lymphomagenesis was not affected. Furthermore, mismatch-directed anti-recombination and sensitivity to methylating agents required Msh2 and Msh6, but not Msh3. Thus, loss of MMR functions specific to Msh2/Msh6 is sufficient for lymphoma development in mice, whereas predisposition to intestinal cancer requires loss of function of both Msh2/Msh6 and Msh2/Msh3.     

Further evidence for the existence of a bottleneck in the metabolism of Saccharomyces cerevisiae

The growth physiology of Saccharomyces cerevisiae strains H1022 and Whi2+ has been studied in aerobic batch and continuous (chemostat) cultures. Results from the measurement of biomass and medium components (off-line) together with oxygen, carbon dioxide and heat measurements (on-line) have been used in an attempt to explore the existence of 'overflow' or 'bottleneck' metabolism as opposed to catabolite repression (Crabtree effect) in these strains. Chemostat experiments indicated that specific oxygen uptake rate (qO2) was linearly related to the dilution rate (D) at values below the critical dilution rate (D crit), becoming constant above D crit, which is in agreement with the bottleneck theory. However, batch culture experiments indicated negligible oxygen consumption during the initial glucose growth phase, the culture exhibiting purely anaerobic metabolism. The bottleneck theory would propose that qO2 has a constant (maximum) value under these conditions. The results presented here suggest that while the bottleneck theory can be adequately used to describe chemostat growth of S. cerevisiae, some other control mechanism must be operating under conditions of high glucose concentrations, such as those initially prevailing in the batch culture experiments.     

Force generation in glycerinated insect-flight muscles without ATP

Zusammenfassung Durch Zugabe und durch Auswaschen von Mg-Pyrophosphat (0,5 mM) oder Mg-Tripoly-Phosphat (1 mM) konnten (in Abwesenheit von ATP) in glyzerinextrahierten Fasern von fibrillären Insektenmuskeln (Lethocerus maximus) reversible Kontraktionszyklen und Änderungen des Dehnungswiderstandes bewirkt werden.

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Supported by Grant No. Ru 154/b of the Deutsche Forschungsgemeinschaft. The excellent technical assistance of Mrs.Helgard Jung is gratefully acknowledged.     

Hendrik Antoon Lorentz und Emil Wiechert

Ohne Zusammenfassung Vorgelegt von S. Flügge