Na 1 Nachlass Max Horkheimer, 564 - Korrespondenzen u.a. mit Alice H. Maier und Leo Löwenthal (p. VI 27, 254-402)

Briefwechsel zwischen Max Horkheimer und Alice H. Maier; 5 Briefe an Maurice und Carolyn Tumarkin von Max Horkheimer, 1957/1964; 3 Briefe zwischen Alice H. Maier und H. P. Edelman, 1957/1963; 2 Briefe von Alice H. Maier an Friedrich Pollock, 1960/1966; 2 Briefe von Max Horkheimer an The Diners Club (New York), 1965; 1 Brief an Patricia und Edward R. Wilbur von Alice H. Maier, 17.05.1965; 2 Briefe von Max Horkheimer an Patricia und Edward R. Wilbur, 1964; 2 Briefe zwischen Alice H. Maier und Alfred L. Copley, 1965; 5 Briefe zwischen William C. Kirkwood und Max Horkheimer, 1964; 2 Briefe von Max Horkheimer an Ulla Posnansky, 1964; 1 Brief an Leo Löwenthal von Max Horkheimer, 23.06.1964; 1 Brief von Max Horkheimer an Amerino Lionetti, 03.06.1964; 10 Briefe zwischen Herbert Marcuse und Max Horkheimer, 1935 - 1936; 1 Brief von R. Piper an Herbert Marcuse, 26.03.1936;

Color data, carbon and oxygen isotopes, and offsets from BBCP Polecat Bench cores 2A and 2B

The Earth's climate abruptly warmed by 5-8 °C during the Palaeocene-Eocene thermal maximum (PETM), about 55.5 million years ago**1,2. This warming was associated with a massive addition of carbon to the ocean-atmosphere system, but estimates of the Earth systemresponse to this perturbation are complicated by widely varying estimates of the duration of carbon release, which range from less than a year to tens of thousands of years. In addition the source of the carbon, and whether it was released as a single injection or in several pulses, remains the subject of debate**2-4. Here we present a new high-resolution carbon isotope record from terrestrial deposits in the Bighorn Basin (Wyoming, USA) spanning the PETM, and interpret the record using a carbon-cycle boxmodel of the ocean-atmosphere-biosphere system.Our record shows that the beginning of the PETMis characterized by not one but two distinct carbon release events, separated by a recovery to background values. To reproduce this pattern, our model requires two discrete pulses of carbon released directly to the atmosphere, at average rates exceeding 0.9 Pg C yr**-1, with the first pulse lasting fewer than 2,000 years.

The Ets transcription factor ERM is Th1-specific and induced by IL-12 through a Stat4-dependent pathway

Interleukin 12 (IL-12)-induced T helper 1 (Th1) development requires Stat4 activation. However, antigen-activated Th1 cells can produce interferon γ (IFN-γ) independently of IL-12 and Stat4 activation. Thus, in differentiated Th1 cells, factors regulated by IL-12 and Stat4 may be involved in IFN-γ production. Using subtractive cloning, we identified ERM, an Ets transcription factor, to be a Th1-specific, IL-12-induced gene. IL-12-induction of ERM occurred in wild-type and Stat1-deficient, but not Stat4-deficient, T cells, suggesting ERM is Stat4-inducible. Retroviral expression of ERM did not restore IFN-γ production in Stat4-deficient T cells, but augmented IFN-γ expression in Stat4-heterozygous T cells. Ets factors frequently regulate transcription via cooperative interactions with other transcription factors, and ERM has been reported to cooperate with c-Jun. However, in the absence of other transcription factors, ERM augmented expression of an IFN-γ reporter by only 2-fold. Thus, determining the requirement for ERM in Th1 development likely will require gene targeting.

Hypotension and inflammatory cytokine gene expression triggered by factor Xa–nitric oxide signaling

The signaling pathway initiated by factor Xa on vascular endothelial cells was investigated. Factor Xa stimulated a 5- to 10-fold increased release of nitric oxide (NO) in a dose-dependent reaction (0.1–2.5 μg/ml) unaffected by the thrombin inhibitor hirudin but abolished by active site inhibitors, tick anticoagulant peptide, or Glu-Gly-Arg-chloromethyl ketone. In contrast, the homologous clotting protease factor IXa or another endothelial cell ligand, fibrinogen, was ineffective. A factor Xa inter-epidermal growth factor synthetic peptide L83FTRKL88(G) blocking ligand binding to effector cell protease receptor-1 inhibited NO release by factor Xa in a dose-dependent manner, whereas a control scrambled peptide KFTGRLL was ineffective. Catalytically active factor Xa induced hypotension in rats and vasorelaxation in the isolated rat mesentery, which was blocked by the NO synthase inhibitor l-NG-nitroarginine methyl ester (l-NAME) but not by d-NAME. Factor Xa/NO signaling also produced a dose-dependent endothelial cell release of interleukin 6 (range 0.55–3.1 ng/ml) in a reaction inhibited by l-NAME and by the inter-epidermal growth factor peptide Leu83–Leu88 but unaffected by hirudin. Maximal induction of interleukin 6 mRNA required a brief, 30-min stimulation with factor Xa, unaffected by subsequent addition of tissue factor pathway inhibitor. These data suggest that factor Xa-induced NO release modulates endothelial cell-dependent vasorelaxation and cytokine gene expression. This pathway requiring factor Xa binding to effector cell protease receptor-1 and a secondary step of ligand-dependent proteolysis may preserve an anti-thrombotic phenotype of endothelium but also trigger acute phase responses during activation of coagulation in vivo.

Identification of 5′-deoxyribose phosphate lyase activity in human DNA polymerase γ and its role in mitochondrial base excision repair in vitro

Mitochondria have been proposed to possess base excision repair processes to correct oxidative damage to the mitochondrial genome. As the only DNA polymerase (pol) present in mitochondria, pol γ is necessarily implicated in such processes. Therefore, we tested the ability of the catalytic subunit of human pol γ to participate in uracil-provoked base excision repair reconstituted in vitro with purified components. Subsequent to actions of uracil-DNA glycosylase and apurinic/apyrimidinic endonuclease, human pol γ was able to fill a single nucleotide gap in the presence of a 5′ terminal deoxyribose phosphate (dRP) flap. We report here that the catalytic subunit of human pol γ catalyzes release of the dRP residue from incised apurinic/apyrimidinic sites to produce a substrate for DNA ligase. The heat sensitivity of this activity suggests the dRP lyase function requires a three-dimensional protein structure. The dRP lyase activity does not require divalent metal ions, and the ability to trap covalent enzyme-DNA complexes with NaBH4 strongly implicates a Schiff base intermediate in a β-elimination reaction mechanism.

A signaling organelle containing the nerve growth factor-activated receptor tyrosine kinase, TrkA

The topology of signal transduction is particularly important for neurons. Neurotrophic factors such as nerve growth factor (NGF) interact with receptors at distal axons and a signal is transduced by retrograde transport to the cell body to ensure survival of the neuron. We have discovered an organelle that may account for the retrograde transport of the neurotrophin signal. This organelle is derived from endocytosis of the receptor tyrosine kinase for NGF, TrkA. In vitro reactions containing semi-intact PC12 cells and ATP were used to enhance recovery of a novel organelle: small vesicles containing internalized NGF bound to activated TrkA. These vesicles were distinct from clathrin coated vesicles, uncoated primary endocytic vesicles, and synaptic vesicles, and resembled transport vesicles in their sedimentation velocity. They contained 10% of the total bound NGF and almost one-third of the total tyrosine phosphorylated TrkA. These small vesicles are compelling candidates for the organelles through which the neurotrophin signal is conveyed down the axon.