Neonatal lethality associated with respiratory distress in mice lacking cytochrome P450 1A2.

Cytochrome P450 1A2 (CYP1A2) is a constitutively expressed hepatic enzyme that is highly conserved among mammals. This protein is primarily involved in oxidative metabolism of xenobiotics and is capable of metabolically activating numerous procarcinogens including aflatoxin B1, arylamines, heterocyclic amine food mutagens, and polycylic aromatic hydrocarbons. Expression of CYP1A2 is induced after exposure to certain aromatic hydrocarbons (i.e., 2,3,7,8-tetrachlorodibenzo-p-dioxin). Direct evidence for a role of CYP1A2 in any physiological or developmental pathway has not been documented. We now demonstrate that mice homozygous for a targeted mutation in the Cyp1a-2 gene are nonviable. Lethality occurs shortly after birth with symptoms of severe respiratory distress. Mutant neonates display impaired respiratory function associated with histological signs of lung immaturity, lack of air in alveoli at birth, and changes in expression of surfactant apoprotein in alveolar type II cells. The penetrance of the phenotype is not complete (19 mutants survived to adulthood out of 599 mice). Surviving animals, although lacking expression of CYP1A2, appear to be normal and are able to reproduce. These findings establish that CYP1A2 is critical for neonatal survival by influencing the physiology of respiration in neonates, thus offering etiological insights for neonatal respiratory distress syndrome.

Gas-phase folding and unfolding of cytochrome c cations.

Water is thought to play a dominant role in protein folding, yet gaseous multiply protonated proteins from which the water has been completely removed show hydrogen/deuterium (H/D) exchange behavior similar to that used to identify conformations in solution. Indicative of the gas-phase accessibility to D2O, multiply-charged (6+ to 17+) cytochrome c cations exchange at six (or more) distinct levels of 64 to 173 out of 198 exchangeable H atoms, with the 132 H level found at charge values 8+ to 17+. Infrared laser heating and fast collisions can apparently induce ions to unfold to exchange at a higher distinct level, while charge-stripping ions to lower charge values yields apparent folding as well as unfolding.

De historie van den Waldensen : ghedeelt in drie deelen där van het eerste handelt van hunnen oorspronck suyver Gheloove ende vervolgingen die sy door geheel Europa, gedürende den tijt van meer als 450. jaren hebben gheleden. Het tweede vervat de historie van de Waldensen, anders genämt de Albigensen. Het derde begrijpt de leere ende discipline welcke sy onderlinghe ghemeyn ghehadt hebben Midsgaders de wederlegginghe vande leere van ... nne weder-partije. ... Vergadert wt d'autheuren, der welcker namen hier nä ghestelt worden, ende in de Fransoysche tale beschreven,

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OGE Form 450 : a review guide /

Mode of access: Internet.

Operator's organizational, DS, GS, and depot maintenance manual : tractor, full tracked, D.E.D., 7500 lb. min. drawbar pull, w/bulldozer blade, back rip scarifier, J.I. Case model M-450, FSN 2410-935-0714.

"December 1969."