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.     

The response of cyclic 3',5'-AMP and cyclic 3',5'-GMP phosphodiesterases to experimental diabetes

Alloxan diabetes caused a decrease in cyclic AMP phosphodiesterase in all affected rat tissues. Cyclic GMP phosphodiesterase activity was, however, decreased in adipose and liver, but increased increased in heart and uterus.     

Renin in mouse but not in rat submandibular glands

Renin was found in the submandibular glands of male Quackenbush mice in concentrations higher than has been reported for any tissue of any strain or species. However, no renin-like activity could e detected in glands from male and female Wistar rats using either pH 5.8 or 7.4 for assay and a radioimmunoassay specific for renin's reaction product, angiotensin I. Rabbit submandibular glands contained renin.     

Neurosecretion and hydroelectrolytic regulation in Artemia salina (author's transl)]

The activity of Artemia protocerebral median neurosecretory cells is stimulated when animals are grown in media whose tonicity is lower than that of sea weater. The substance liberated by these cells could regulate the tonicity of the internal medium.     

Die Nobelpreise für Medizin-Physiologie,Chemie und Physik

Ohne Zusammenfassung     

Zur Frage der Natur der Ablagerungen in den Gichtknoten

Summary A gout-tophus, which we examined by X-rays and micro-crystallographic methods was definitely proved to be a deposit of monosodiumurate-monohydrate in the form of crystals which could just be detected under the microscope.     

Measurements on the electrical resistivity of thin nickel films

Résumé Dans une publication antérieure, nous avions signalé que le coefficient de température de la résistance électrique des films en nickel était négatif en dessous d'une certaine épaisseur critique (40 mµ). Au-dessus de 40 mµ, la courbe «Résistance en fonction de la température» présentait un minimum aux basses températures. A la suite de nouvelles expériences, nous avons constaté que ce phénomène est accompagné d'une déviation de la loi d'Ohm: la résistance diminue quand le courant de mesure augmente. Nous avons pu conclure que ces deux particularités ne sont qu'indirectement provoquées par la minceur des films. La cause principale est leur état de cristallisation imparfaite. En effet, après avoir subi un échauffement à 150° C pendant plusieurs heures, le coefficient de température négatif change de signe (le minimum disparaît) et la loi d'Ohm est respectée.

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Research-fellow of the Belgian «Fonds National de la Recherche Scientifique»     

Embryonic exposure to hyper glucocorticoids suppresses brown fat development and thermogenesis via REDD1

Maternal stress during pregnancy is prevailing worldwide,which exposes fetuses to intrauterine hyper glucocorticoids (GC),programming offspring to obesity and m...