p73 regulates basal and starvation-induced liver metabolism in vivo

As a member of the p53 gene family, p73 regulates cell cycle arrest, apoptosis, neurogenesis, immunity and inflammation. Recently, p73 has been shown to transcriptionally regulate selective metabolic enzymes, such as cytochrome c oxidase subunit IV isoform 1, glucose 6-phosphate dehydrogenase and glutaminase-2, resulting in significant effects on metabolism, including hepatocellular lipid metabolism, glutathione homeostasis and the pentose phosphate pathway. In order to further investigate the metabolic effect of p73, here, we compared the global metabolic profile of livers from p73 knockout and wild-type mice under both control and starvation conditions. Our results show that the depletion of all p73 isoforms cause altered lysine metabolism and glycolysis, distinct patterns for glutathione synthesis and Krebs cycle, as well as an elevated pentose phosphate pathway and abnormal lipid accumulation. These results indicate that p73 regulates basal and starvation-induced fuel metabolism in the liver, a finding that is likely to be highly relevant for metabolism-associated disorders, such as diabetes and cancer.

A novel mutation in BCS1L associated with deafness, tubulopathy, growth retardation and microcephaly

We report a novel homozygous missense mutation in the ubiquinol-cytochrome c reductase synthesis-like (BCS1L) gene in two consanguineous Turkish families associated with deafness, Fanconi syndrome (tubulopathy), microcephaly, mental and growth retardation. All three patients presented with transitory metabolic acidosis in the neonatal period and development of persistent renal de Toni-Debré-Fanconi-type tubulopathy, with subsequent rachitis, short stature, microcephaly, sensorineural hearing impairment, mild mental retardation and liver dysfunction. The novel missense mutation c.142A>G (p.M48V) in BCS1L is located at a highly conserved region associated with sorting to the mitochondria. Biochemical analysis revealed an isolated complex III deficiency in skeletal muscle not detected in fibroblasts. Native polyacrylamide gel electrophoresis (PAGE) revealed normal super complex formation, but a shift in mobility of complex III most likely caused by the absence of the BCS1L-mediated insertion of Rieske Fe/S protein into complex III. These findings expand the phenotypic spectrum of BCS1L mutations, highlight the importance of biochemical analysis of different primary affected tissue and underline that neonatal lactic acidosis with multi-organ involvement may resolve after the newborn period with a relatively spared neurological outcome and survival into adulthood. CONCLUSION Mutation screening for BCS1L should be considered in the differential diagnosis of severe (proximal) tubulopathy in the newborn period. What is Known: • Mutations in BCS1L cause mitochondrial complex III deficiencies. • Phenotypic presentations of defective BCS1L range from Bjornstad to neonatal GRACILE syndrome. What is New: • Description of a novel homozygous mutation in BCS1L with transient neonatal acidosis and persistent de Toni-Debré-Fanconi-type tubulopathy. • The long survival of patients with phenotypic presentation of severe complex III deficiency is uncommon.

NADPH-CYTOCHROME P-450 REDUCTASE: EVIDENCE FOR TWO SEPARATE STRUCTURAL DOMAINS AND ISOLATION AND CHARACTERIZATION OF THE MEMBRANE ASSOCIATED SEGMENT

Homogenous detergent-solubilized NADPH-Cytochrome P-450 reductase was incorporated into microsomes and liposomes. This binding occurred spontaneously at temperatures between 4(DEGREES) and 37(DEGREES) and appeared to involve hydrophobic forces as the binding was not disrupted by 0.5 M sodium chloride. This exogenously-added reductase was active catalytically towards native cytochrome P-450, suggesting an association with the microsomal membrane similar to endogenous reductase. Homogeneous detergent-solubilized reductase was disaggregated by Renex-690 micelles, confirming the presence of a hydrophobic combining region on the enzyme. In contrast to these results, steapsin protease-solubilized reductase was incapable of microsomal attachment and did not interact with Renex-690 micelles. Detergent-solubilized reductase (76,500 daltons) was converted into a form with the electrophoretic mobility of steapsin protease-solubilized reductase (68,000 daltons) and a 12,500 dalton peptide (as determined by polyacrylamide-SDS gel electrophoresis) when the liposomal-incorporated enzyme was incubated with steapsin protease. The 68,000 dalton fragment thus obtained had properties identical with steapsin protease-solubilized reductase, i.e. it was catalytically active towards cytochrome c but inactive towards cytochrome P-450 and did not bind liposomes. The 12,500 dalton fragment remained associated with the liposomes when the digest was fractionated by gel filtration, suggesting that this is the segment of the enzyme which is embedded in the phospholipid bilayer. Thus, detergent-solubilized reductase appears to contain a soluble catalytic domain and a separate and separable membrane-binding domain. This latter domain is required for attaching the enzyme to the membrane and also to facilitate the catalytic interaction between the reductase and its native electron acceptor, cytochrome P-450. The membrane-binding segment of the reductase was isolated by preparative gel electrophoresis in SDS following its generation by proteolytic treatment of liposome-incorporated reductase. The peptide has a molecular weight of 6,400 as determined by gel filtration in 8 M guanidine hydrochloride and has an amino acid composition which is not especially hydrophobic. Following removal of SDS and dialysis out of 6 M urea, the membrane-binding peptide was unable to inhibit the activity of a reconstituted system containing purified reductase and cytochrome P-450. Moreover, when reductase and cytochrome P-450 were added to liposomes which contained the membrane-binding peptide, it was determined that mixed function oxidase activity was reconstituted as effectively as when vesicles without the membrane-binding peptide were used. Thus, the membrane-binding peptide was ineffective as an inhibitor of mixed function oxidase activity, suggesting perhaps that it facilitates catalysis by anchoring the catalytic domain of the reductase proximal to cytochrome P-450 (i.e. in the same mixed micelle) rather than through a specific interaction with cytochrome P-450. ^

CHARACTERIZATION OF CYTOCHROME P-450 MIXED FUNCTION OXIDASE OF RAT COLON MUCOSA

Non-pregnant, female adult rats pretreated with either phenobarbital (PB) or (beta)-naphthoflavone ((beta)NF) through short-course intraperitoneal injections were shown by sodium dithionite-reduced carbon monoxide difference spectroscopy and NADPH-cytochrome c in vitro assay to contain cytochrome P-450 and NADPH-dependent reductase associated with the microsomal fraction of colon mucosa. These two protein components of the mixed function oxidase system were released from the microsomal membrane, resolved from each other, and partially purified by using a combination of techniques including solubilization in nonionic detergent followed by ultracentrifugation, anion exchange and adsorption column chromatographies, native gel electrophoresis, polyethylene glycol fractionation and ultrafiltration.^ In vitro reconstitution assays demonstrated the cytochrome P-450 fraction as the site of substrate and molecular oxygen binding. By the use of immunochemical techniques including radial immunodiffusion, Ouchterlony double diffusion and protein electroblotting, the cytochrome P-450 fraction was shown to contain at least 5 forms of the protein, having molecular weights as determined by SDS gel electrophoresis identical to the corresponding hepatic cytochrome P-450. Estimation of total cytochrome P-450 content confirmed the preferential induction of particular forms in response to the appropriate drug pretreatment.^ The colonic NADPH-dependent reductase was isolated from native gel electrophoresis and second dimensional SDS gel electrophoresis was performed in parallel to that for purified reductase from liver. Comparative electrophoretic mobilities together with immunochemical analysis, as with the cytochrome P-450s, reconstitution assays, and kinetic characterization using artificial electron acceptors, gave conclusive proof of the structural and functional homology between the colon and liver sources of the enzyme.^ Drug metabolism was performed in the reconstituted mixed function oxidase system containing a particular purified liver cytochrome P-450 form or partially pure colon cytochrome P-450 fraction plus colon or liver reductase and synthetic lipid vesicles. The two drugs, benzo{(alpha)}pyrene and benzphetamine, which are most representative of the action of system in liver, lung and kidney, were tested to determine the specificity of the reconstituted system. The kinetics of benzo{(alpha)}pyrene hydroxylation were followed fluorimetrically for 3-hydroxybenzo{(alpha)}pyrene production. . . . (Author's abstract exceeds stipulated maximum length. Discontinued here with permission of author.) UMI ^

Lindane induced cellular dysfunction in MDCK cells: The role of the peripheral benzodiazepine receptor

The central nervous system GABAA/Benzodiazepine (GABAA/BZD) receptors are targets for many pharmaceutical agents and several classes of pesticides. Lindane is an organochlorine pesticide, although banned from production in the U.S. since 1977, still imported for use as an insecticide and pharmaceutically to control ectoparasites (ATSDR, 1994). Lindane functions as a GABA/BZD receptor antagonist within the central nervous system (CNS). Outside of the CNS, peripheral BZD receptors have been localized to the distal tubule of the kidney. Previous research in our laboratory has shown that incubation of renal cortical slices with lindane can produce an increase in kallikrein leakage, suggesting a distal tubular effect. In this study, Madin Darby Canine Kidney (MDCK) cells were used as an in vitro system to assess the toxicity of lindane. This purpose of this study was to determine if interactions between a renal distal tubular BZD-like receptor and lindane could lead to perturbations in renal distal cellular chloride (Cl−) transport and mitochondrial dysfunction and ultimately, cellular death. ^ Pertubations in renal chloride transport were measured indirectly by determining if lindane altered cell function responsiveness following osmotic stress. MDCK cells pre-treated with lindane and then subjected to osmotic stress remained swollen for up to 12 hours post-stress. Lindane-induced dysfunction was assessed through stress protein induction measured by Western Blot analysis. Lindane pretreatment delayed Heat Shock Protein 72 (HSP72) induction by 36 hours in osmotically stressed cells. Pretreatment with 1 × 10 −5 M LIN followed by osmotic stress elevated p38 and Stress Activated Protein Kinase (SAPK/JNK) at 15 minutes which declined at 30 minutes. Lindane appeared to have no effect on Endoplasmic Reticulum Related Kinase (ERK) induction. Lindane did not effect osmotically stressed LLC-PKI cells, a control cell line. ^ Lindane-treated MDCK cells did not exhibit necrosis. Instead, apoptosis was observed in lindane-treated MDCK cells in both time- and dose-dependent manners. LLC-PKI cells were not affected by LIN treatment. ^ To better understand the mechanism of lindane-induced apoptosis, mitochondrial function was measured. No changes in cytochrome c release or mitochondrial membrane potential were observed suggesting the mitochondrial pathway was not involved in lindane-induced apoptosis. ^ Further research will need to be conducted to determine the mechanism of lindane-induced adverse cellular effects. ^

Integrin mediated growth and apoptosis in human gastric adenocarcinoma

Integrins are important as the primary cell adhesion molecule providing information about the extracellular microenvironment to the interior of the cell to influence cellular behavior such as differentiation, proliferation and apoptosis. Apoptotic death due to loss of adhesion is termed anoikis. In this study we have obtained a parental human gastric adenocarcinoma cell line that yielded two variant lines that had differing responses to lack of adhesion. The STAD.APO cell line undergoes apoptosis when denied adherence and the STAD.ARR cell line enters into cell cycle arrest under the identical suspended conditions. We have shown that cyclin A and cyclin D mRNA and protein are down regulated when cells are denied adherence for 24 hours in tissue culture wells previously coated with poly-HEMA. To test whether cyclin A was able to rescue cells from cell cycle arrest and/or anoikis by overriding the cell cycle machinery we transfected the full length cDNA in to each cell type. Surprisingly we found that anoikis and cell cycle arrest due to suspended conditions was not affected by overexpression of cyclin A protein, but that growth under adhered conditions was reduced compared to vector alone control transfectants. Further, we transfected other cell lines; ST7, gastric cancer, MDA-MB-4.35, breast cancer, and HPB T-cell leukemic and in no case were suspended culturing conditions overcome by cyclin A. This result indicates an additional level of regulation for the cell cycle machinery. Additionally, soluble collagen was shown to be able to save from anoikis and also from cell cycle arrest while the β1 specific mAb 33B6 was only able to save from anoikis. Immunofluorescent studies show that soluble collagen creates clusters of β1 with FAK and also β1 with actin in the STAD.ARR cells but does not in the STAD.APO cells. This result indicates that the phenotypes under suspended conditions between these cell lines may diverge at their requirements for integrin ligation. Additionally we characterized the nature of anoikis by showing cytochrome c release, caspase 3, p21 and p53 activation in STAD.APO cells. Thus, our results have implications in the understanding of integrin biology and neoplastic progression. ^

Use of cardiac glycosides for treatment of cancer: Determinants of cancer cell sensitivity

Cardiac glycoside compounds have traditionally been used to treat congestive heart failure. Recently, reports have suggested that cardiac glycosides may also be useful for treatment of malignant disease. Our research with oleandrin, a cardiac glycoside component of Nerium oleander, has shown it to be a potent inducer of human but not murine tumor cell apoptosis. Determinants of tumor sensitivity to cardiac glycosides were therefore studied in order to understand the species selective cytotoxic effects as well as explore differential sensitivity amongst a variety of human tumor cell lines. ^ An initial model system involved a comparison of human (BRO) to murine (B16) melanoma cells. Human BRO cells were found to express both the sensitive α3 as well as the less sensitive α1 isoform subunits of Na+,K +-ATPase while mouse B16 cells expressed only the α1 isoform. Drug uptake and inhibition of Na+,K+-ATPase activity were also different between BRO and B16 cells. Partially purified human Na+,K+-ATPase enzyme was inhibited by cardiac glycosides at a concentration that was 1000-fold less than that required to inhibit mouse B16 enzyme to the same extent. In addition, uptake of oleandrin and ouabain was 3–4 fold greater in human than murine cells. These data indicate that differential expression of Na+,K+-ATPase isoform composition in BRO and B16 cells as well as drug uptake and total enzyme activity may all be important determinants of tumor cell sensitivity to cardiac glycosides. ^ In a second model system, two in vitro cell culture model systems were investigated. The first consisted of HFU251 (low expression of Na+,K+-ATPase) and U251 (high Na+ ,K+-ATPase expression) cell lines. Also investigated were human BRO cells that had undergone stable transfection with the α1 subunit resulting in an increase in total Na+,K+-ATPase expression. Data derived from these model systems have indicated that increased expression of Na+,K+-ATPase is associated with an increased resistance to cardiac glycosides. Over-expression of Na +,K+-ATPase in tumor cells resulted in an increase of total Na+,K+-ATPase activity and, in turn, a decreased inhibition of Na+,K+-ATPase activity by cardiac glycosides. However, of interest was the observation that increased enzyme expression was also associated with an elevated basal level of glutathione (GSH) within cells. Both increased Na+,K+-ATPase activity and elevated GSH content appear to contribute to a delayed as well as diminished release of cytochrome c and caspase activation. In addition, we have noted an increased colony forming ability in cells with a high level of Na+,K+-ATPase expression. This suggests that Na+,K+-ATPase is actively involved in tumor cell growth and survival. ^

Mechanism of N-(4-hydroxyphenyl)retinamide (4HPR)-induced apoptosis in head and neck squamous cell carcinoma cells

4HPR is a synthetic retinoid that has shown chemopreventive and therapeutic efficacy against premalignant and malignant lesions including oral leukoplakia, ovarian and breast cancer and neuroblastoma in clinical trials. 4HPR induces growth inhibition and apoptosis in various cancer cells including head and neck squamous cell carcinoma (HNSCC) cells. 4HPR induces apoptosis by several mechanisms including increasing reactive oxygen species (ROS), or inducing mitochondrial permeability transition (MPT). 4HPR has also been shown to modulate the level of different proteins by transcriptional activation or posttranslational modification in various cellular contexts. However, the mechanism of its action is not fully elucidated. In this study, we explored the mechanism of 4HPR-induced apoptosis in HNSCC cells. ^ First, we identified proteins modulated by 4HPR by using proteomics approaches including: Powerblot western array and 2-dimensional polyacrylamide gel electrophoresis. We found that 4HPR modulated the levels of several proteins including c-Jun. Further analysis has shown that 4HPR induced activation of Activator Protein 1 (AP-1) components, c-Jun and ATF-2. We also found that 4HPR increased the level of Heat shock protein (Hsp) 70 and phosphorylation of Hsp27. ^ Second, we found that 4HPR induced prolonged activation of JNK, p38/MAPK and extracellular signal-regulated kinase (ERK). We also demonstrated that the activation of these kinases is required for 4HPR-induced apoptosis. JNK inhibitor SP600125 and siRNA against JNK1 and JNK2 suppressed, while overexpression of JNK1 enhanced 4HPR-induced apoptosis. p38/MAPK inhibitor PD169316 and MEK1/2 inhibitor PD98059 also suppressed 4HPR-induced apoptosis. We also demonstrated that activation of JNK, p38/MAPK and ERK is triggered by ROS generation induced by 4HPR. We also found that translation inhibitor, cycloheximide, suppressed 4HPR-induced apoptosis through inhibition of 4HPR-induced events (e.g. ROS generation, cytochrome c release, JNK activation and suppression of Akt). We also demonstrated that MPT is involved in 4HPR-induced apoptosis. ^ Third, we demonstrated the presence of NADPH oxidase in HNSCC 2B cells. We also found that 4HPR increased the level of the p67phox, a subunit of NADPH oxidase which participates in ROS production and apoptosis induced by 4HPR. ^ The novel insight into the mechanism by which 4HPR induces apoptosis can be used to improve design of future clinical studies with this synthetic retinoid in combination with specific MAPK modulators. ^

Function of cardiolipin in mitochondria of Saccharomyces cerevisiae

Cardiolipin and its precursor phosphatidylglycerol, phospholipids found uniquely in membranes engaged in oxidative phosphorylation, play important roles in multimeric complexes of the energy transducing system (ETS) associated with the inner mitochondrial membrane. A combined molecular genetic and biochemical approach was used to more precisely define the role of cardiolipin in cell processes. ^ Strains of yeast Saccharomyces cerevisiae unable to synthesize cardiolipin because of the crd1Δ allele (encodes cardiolipin synthase) with different phenotypes were analyzed to determine which phenotypes are due to lack of cardiolipin. We concluded that many of the severe phenotypes ascribed to cells lacking cardiolipin, particularly when grown at 37°C, are because of the synergistic interaction of the crd1Δ mutation with the reduced expression of the PET56 gene which encodes a component essential for the formation of functional mitochondrial ribosomes. We also demonstrate that much of the reduced mitochondrial function in crd1Δ is because of reduced expression of ETS components at elevated temperature. ^ A crd1Δ mutant of S. cerevisiae has less severe physiological changes than strains lacking both phosphatidylglycerol and cardiolipin due to an increased level of phosphatidylglycerol, which might partially substitute for the cardiolipin-requiring functions. By varying the level of cardiolipin, we were able to correlate phenotypes in a dose-dependent manner with the level of cardiolipin to support more strongly an involvement of cardiolipin in a particular cellular process. There is almost complete lack of a supercomplex composed of cytochrome bc1 complex (complex III) and cytochrome c oxidase (complex IV) in extracts of cardiolipin-lacking mitochondria when compared to wild type cells and the level of supercomplex varies in proportion to the cardiolipin levels. Reduced cardiolipin levels also compromise the growth properties of yeast in a dose-dependent manner suggesting that the loss in growth efficiency is related to a role of cardiolipin that cannot be replaced by phosphatidylglycerol. An independent kinetic approach was performed to compare organization of the respiratory chain in wild-type and cardiolipin-lacking mitochondria. Cardiolipin-lacking mitochondria display kinetic properties for electron transfer between complexes III and IV via cytochrome c consistent with cytochrome c being a freely diffusible carrier, confirming complexes III and IV exist as individual complexes and not associated into a supercomplex in cardiolipin-lacking mitochondria. ^

Na 1 Nachlass Max Horkheimer, 642 - "Materialien. Druckseiten aus Zeitschriften", "Menschen im Großbetrieb" und "Vorwort zu: 'Zeugnisse. Theodor W. Adorno zum 60. Geburtstag'" (p. IX 20.11-76-IX 22)

11. Salomon, Albert: "The Spirit of the Soldier and Nazi Militarism". Social Research, Februar 1942, 13 Blatt; 12. Dicks, H.V.: "The Psychological Foundations of the Wehrmacht". Als Typoskript vervielfältigt, 42 Blatt; 13. Clark, Robert A.: "Aggressivness and Military Training". American Journal of Sociology, Volume 51, Number 5, March 1946, 5 Blatt; 14. Stagner, Ross: "Fascist Attitudes: Their Determening Conditions". The Journal of Social Psychology, Volume III, Number 4, 1936, 9 Blatt; 15. Apple, Kenneth E.: "Nationalism and Souvereignity: A Psychiatric View." The Journal of Normal and Abnorma Psychology, Volume 40, Number 4, October 1945, 4 Blatt; 16. Schreier, Fritz: "German Aggressivness- Its Reasons and Types". Journal of Normal and Abnormal Psychology, Volume 38, Number 2, April 1943, 7 Blatt; 17. Stagner, Ross: "Fascist Attitudes: An Exploratory Study". The Journal of Social Psychology, Volume III, Number 3, 1936, 6 Blatt; 18. Stagner, Ross und Katzoff, E. T.: "Fascist Attitudes: Factor Analysis of Item Correlations". The Journal of Social Psychology, 16, 1942, 4 Blatt; 19. Stagner, Ross und Osgood, Charles E.: "Impact of War on a Nationalistic Frame of Reference". The Journal of Social Psychology, 24, 1946, 15 Blatt; 20. Day, Daniel Droba und Quackenbusch, O.F.: Attitudes Towards Defensive, Cooperative and Aggressive War". The Journal of Social Psychology, 16, 1942, 5 Blatt; 21. Kecskemeti, Paul und Leites, Nathan: "Some Psychological Hypotheses on Nazi Germany: I". The Journal of Social Psychology, 26, 1947, 22 Blatt; 22. Dieselben: "Some Psychological Hypotheses on Nazi Germany: II". Ebenda, 27, 1948, 14 Blatt; 23. Parsons, Tollcott: "Certain Primary Sources and Pattersens of Aggression in the Social Structure of the Western World". Psychiatry, Volume 10, Number 2, May 1047, 8 Blatt; 24. Zerner, Elizabeth H.: "German Occupation and Anti-Semitism in France". Public Opinion Quarterly, Summer 1948, 5 Blatt; 25. Hauser, Ernest O.: "Doctor [Julian] Huxley`s Wonderful Zoo". The Saturday Evening Post, ohne Datum, 5 Blatt; 26. Zeitungsabschnitt, 1 Blatt; "Menschen im Großbetrieb" (GS 8, S. 95-105); Veröffentlicht in: Deutsche Zeitung, 19.02.1955. a) Typoskript mit dem Titel "Meinungsforschung im Betrieb" mit handschriftlichen Korrekturen, 10 Blatt b) Typoskript mit dem Titel "Der Mensch im Großbetrieb", mit eigenhändigen Korrekturen und einer handschriftlichen Notiz von Theodor W. Adorno, 17 Blatt c) Typoskript mit eigenhändigen Korrekturen, 17 Blatt d) Zeitungsdruck mit dem Titel "Menschen im Großbetrieb", mit eigenhändigen Korrekturen, 1 Blatt e)-f) Dasselbe , 1 Blatt; "Vorwort" zu: "Zeugnisse. Theodor W. Adorno zum 60. Geburtstag"; Veröffentlicht: Ebenda, Frankfurt am Main, 1963. a)-b) Typoskript mit eigenhändigen Korrekturen, 1 Blatt c) Typoskript, 2 Blatt;

Na 1 Nachlass Max Horkheimer, 655 - Vorträge über Antisemitismus (p. IX 40.1-2-IX 48.1-2)

"Summer institute on Modern European Culture" (1947?); 1. Ankündigung für eine Vorlesungsreihe von Max Horkheimer, Theodor W. Adorno, Leo Löwenthal, Herbert Marcuse, Friedrich Pollock. a) Typoskript mit eigenhändigen Ergänzungen, 20 Blatt b) Typoskript mit handschriftlichen Ergänzungen, 19 Blatt; 2. Herbert Marcuse: "Philosophie allemande et francaise 1871-1933". Typoskript mit eigenhändigen Korrekturen, 18 Blatt; "Tentative Program for the Course of Antisemitism". Vorlesungsankündigung 1948 von Max Horkheimer, Theodor W. Adorno, Friedrich Pollock. Typoskript 2 Blatt; Max Horkheimer: Bericht über die Antisemitismus-Forschungen des Instituts für Sozialforschung (GS 12, S. 165-171). Vortrag gehalten am 16.4.1943, englischer Text. a) Typoskript mit eigenhändigen Korrekturen, 5 Blatt b) Typoskript mit eigenhändigen Korrekturen, 8 Blatt c) Typoskript mit handschriftlichen Korrekturen, 8 Blatt; Max Horkheimer: Bericht über die Antisemitismus-Forschungen des Instituts für Sozialforschung (GS 12, S. 172-183). Vortrag gehalten am 30.4.1943, Temple Israel. a) Typoskript mit eigenhändigen Korrekturen und Ergänzungen, 12 Blatt b) Typoskript mit handschriftlichen Korrekturen, 11 Blatt c) Typoskript mit eigenhändigen Korrekturen, 14 Blatt; Max Horkheimer: Über die Psychologie des Judentums und des Antisemitismus; 1. Vortrag, gehalten am 7.10.1943 im Department of Psychology, UCLA, eigenhändige Notizen, 1 Blatt; 2. Auszüge aus Schriften und Arbeitspapieren von: G.M. Davidson, Salomon Andhil Fineberg, A.R.L. Gurland, Oscar I. Janomsky, Paul W. Massing, Typoskript mit eigenhändigen Ergänzungen, 8 Blatt; Max Horkheimer: Anti-Semitism as a Social Phenomenon (GS 5, S.364-372); 1. Vortrag, gehalten am 17.6.1944 in San Francisco, Psychoanalytic Society, veröffentlicht unter dem Titel 'Sociological Background of the Psychoanalytic Approach". In: Ernst Simmel (ed.), "Anti-Semitism. A Social Disease", New York, 1946, S.1-10. a) Typoskript, 13 Blatt, b) Teilstück, Typoskript, 1 Blatt, c) Teilstück, Typoskript mit eigenhändigen Korrekturen, 2 Blatt d) Typoskript mit handschriftlichen Korrekturen, 9 Blatt; 2. "Notes to the Speech in San Francisco", Notizen, 4 Blatt; 3. eigenhändige Notizen zum Vortrag, 5 Blatt; 4. Rede für Maurice Karpf, Typoskript mit eigenhändigen Korrekturen, 2 Blatt; 5. Theodor W. Adorno: "Mammoth Motives", Notizen zum Verhältnis von Soziologie und Psychologie des Antisemitismus, 3 Blatt; 6. Theodor W. Adorno: "Patterns of Anti-Democratic Propaganda", veröffentlicht in: Ernst Simmel, "Anti-Semitism. A Social Disease", New York, 1946, S.125-137. a) Typoskript, 15 Blatt, b) Typoskript, 14 Blatt;; 7. Einladung, Drucksache, 2 Blatt; 8. Max Horkheimer: 2 Brief an Donald MacFerlane, Pacific Palisades, 22.5.1944, 1 Blatt; Max Horkheimer: Vorträge 1944-45; 1. "Report for the N.C.R.A.C.". Über Forschungsprojekte des American Jewish Committee and des American Jewish Congress, vorgetragen am 14.1.1944, Typoskript, 4 Blatt; 2. Notizen zu 1: Über Kurt Lewin, Typoskript, 3 Blatt; 3. eigenhändige Notizen zu 1., 3 Blatt; 4. Über die europäische Tradition der Arbeiten des Instituts für Sozialforschung. Vortrag, gehalten am 8.12.1944. Eigenhändige Notizen, 1 Blatt; 5. Über psychologische Aspekte der Antisemitismusforschung des Instituts für Sozialforschung. Vortrag, gehalten am 19.4.1945. Eigenhändige Notizen, 2 Blatt; 6. Über sozioökonomische Aspekte des Antisemitismus in Europa und in der Arbeiterschaft der USA. Vortrag, gehalten am 8.6.1945. Psychosomatic Society a) Notizen zum Vortrag, 4 Blatt, b) eigenhändige Notizen, 3 Blatt; 7. Notizen zu 6., Typoskript, 17 Blatt,; 8. Notizen zu 6. "Quotations from Labor Study", Typoskript, 12 Blatt; 9. Über neue Forschungsprojekte des Instituts für Sozialforschung zum Antisemitismus. Vortrag, gehalten am 24.10.1945. Eigenhändige Notizen, 2 Blatt; 10. Über Antisemitismus. Vortrag, gehalten am 3.12.1945. Eigenhändige Notizen, 2 Blatt; 11.-15. Vorträge über Antisemitismus. Datierung unklar (etwa 1945) (u.a. "Mountvernon Speech" und "Breakfast Speech"), 17 Blatt; 16. Über Judentum und Katholizismus in der neueren Geschichte. Eigenhändige Notizen zu einem Vortrag, Datierung unklar, 3 Blatt; 17. Über Vorurteil, Vortrag oder Diskussion in einer Synagoge, Datierung unklar, eigenhändige Notizen, 1 Blatt; Max Horkheimer: Über die Antisemitismus-Forschungen des Instituts für Sozialforschung. Vortrag, gehalten beim U.C.R.A.C.-Meeting, 15.-17.6.1946, Chicago:; 1. eigenhändige Notizen, 13 Blatt; 2. Fragebogen, als Typoskript vervielfältigt, mit eigenhändigen Ergänzungen, 6 Blatt;

Na 1 Nachlass Max Horkheimer, 686 - Rosenzweig-Test, "Art Project on Fascist Agitator" (p. IX 148.1-2 - IX 149.1-7)

Zum Rosenzweig-Test, 1945; Brown, J.F.: "Memorandum on the Modification of the Rosenzweig Picture Frustration Test". Typoskript, 3 Blatt; Rosenzweig, Saul. "The Picture-Association Method and Its Application in a Study of Reactions to Frustration.", Sonderdruck aus: Journal of Personality, September 1945, S. 3-23; Materialien zum "Art Project on Fascist Agitator" (1945):; 1. "What is a Fascist Agitator?", a) Typoskript, 1 Blatt, b) Typoskript mit handschriftlichen Korrekturen, 2 Blatt; 2. "Some Traits of the Fascist Agitator". Typoskript, 5 Blatt; 3. "Pamphlet", a) Typoskript, 1 Blatt, b) Typoskript, 1 Blatt, c) Typoskript mit dem Titel 'Devices of the Agitator', 1 Blatt; 4. Max Horkheimer: eigenhändige Notizen über den Agitator, 1 Blatt; 5. "Quotes from the Agitator (pages refer to Leo Löwenthals manuscript vol. III)". Typoskript, 7 Blatt; 6. Adressenlisten, 3 Blatt; 7. Materialien zum 'Agitator-Projekt': Photos, Reproduktionen von Zeichnungen und Zeitungsausschnitten;

Na 1 Nachlass Max Horkheimer, 695 - "The Collapse of German Democracy and the Expansion of National Socialism", "Cultural Aspects of National Socialism" u.a. (p. IX 169.1a - IX 170.1-4)

"The Collapse of German Democracy and the Expansion of National Socialism" (1940):; 1. Darstellung des Forschungsprojekts (15.9.1940), b. Typoskript mit handschriftlichen Korrekturen, 78 Blatt; 2. "Research work on recent trends in the history of ideas (parts of the Research project on the Collapse of German Democracy would be included)". Als Memorandum zur Eröffnung zur Eröffnung einer Zweigstelle des Instituts in Los Angeles (12.12.1940): a) Typoskript, 2 Blatt, b) Teilstück, Typoskript mit handschriftlichen Korrekturen, 1 Blatt, c) Teilstück, Typoskript mit handschriftlichen Korrekturen, 1 Blatt, d) Teilstück, Typoskript, 1 Blatt, e) Teilstück, Typoskript, 1 Blatt, f) Entwurf, Typoskript mit handschriftlichen Korrekturen und Manuskript, 3 Blatt; 3. University of California, Los Angeles: 2 Briefe (Abschrift) von Max Horkheimer, o.O., 1940, 2 Briefe (Abschrift) an Max Horkheimer, 1940, 2 Blatt; A.R.L. Gurland: "Survey of Structural Changes in the German Economy, 1933 to 1939. Technological Bases and Organizational Forms of the National Socialist Economic System". Typoskript mit handschriftlichen Korrekturen unter anderem von Theodor W. Adorno, 48 Blatt (formal nicht identisch mit "Technological Trends and Economic Structure under National Socialism", Studies in Philosophy and Social Science, Bd. IX, 1941, S. 226ff.); "Cultural Aspects of National Socialism. A Research Project" (1941):; 1. Institute of Social Research: Mitteilung über das Forschungsprojekt und das 'Supplementary Statement', Typoskript, englisch, 4 Blatt; 2. Supplementary Statement to the Research Project, a) Typoskript, 14.4.1941, 63 Blatt, b) Typoskript, 12.4.1941, mit handschriftlichen Korrekturen, 35 Blatt; 3. "Cultural Aspects of National Socialism. A Research Project" (24.2.1941), a) als Typoskript vervielfältigt, 54 Blatt, b) Typoskript mit handschriftlichen Korrekturen, 34 Blatt, c) Fassung Januar 1941, Typoskript mit handschriftlichen Korrekturen, 40 Blatt; 4. Inhaltsverzeichnisse, mit handschriftlichen Korrekturen, 3 Blatt;

Na 1 Nachlass Max Horkheimer, 707 - "German Refugees from Eastern Zone" (p. IX 183.1-2 - IX 184.2-18)

"German Refugees from the Eastern Zone" 1952; 1. "Outline of a Pilot Study of German Refugees from the Eastern Zone Who are presently in Berlin" a) Typoskript, 4 Blatt; b) Typoskript, 3 Blatt; 2. "Budget for a Pilot Study of German Refugees from the Eastern Zone in Berlin" a) 2 Blatt; b) 1 Blatt; c) 1 Blatt; d) 1 Blatt; "Universität und Gesellschaft" 1952-1956; 1. "Universität und Gesellschaft" Teil III: Expertenbefragung. Forschungsbericht, 1953; als Typoskript vervielfältigt und gebunden, 77 Blatt; 2.-7. Allgemeine Darstellung der Untersuchungen; 2. "Einige wichtige Ergebnisse der Universitätsstudie", 1956. Als Typoskript vervielfältigt, 5 Blatt; 3. "Vorläufige Gliederung für den Bericht der Hochschul-Untersuchung" 2 Blatt; 4. "The German University of Today. Progress Report on a Research Project" 02.11.1955 a) Typoskirpt, 12 Blatt; b) Typoskript mit handschriftlichen Korrekturen, 12 Blatt; 5. "The German University of Today. A Progress Report on a Research Project" a) Typoskript, 7 Blatt; b) Typoskript mit handschriftlichen Korrekturen, 8 Blatt; c) Typoskirpt mit handschriftlichen Korrekturen, 12 Blatt; 6. "Funktion und Wirklichkeit der Universität heute. Zwischenbericht über drei Studien des Instituts für Sozialforschung an der Johann Wolfgang Goethe- Universität". Typoskript, 25 Blatt; 7. "Pläne einer Untersuchung über die Vorstellung von der Finktion der heutigen deutschen Universität bei bestimmten Personenkreisen" a) Typoskirpt, 11 Blatt; b) Typoskript, 11 Blatt; 8.-10. Studentenbefragung; 8. Fagebogen zur Umfrage "Warum studieren Studenten?", als Typoskript vervielfältigt, 19 Blatt; 9. "The Economic Situation of Students at the Johann Wolfgang Goethe- University in Frankfurt am Main" Resultate der Umfrage vom Winter 1952/43; Januar 1956; a) Typoskript, 43 Blatt; b) 43 Blatt; 10. "Students and Parentl Influence. Results of a Survey" a) Typoskript, 25 Blatt; b) Typoskript mit handschriftlichen Korrekturen von Frederick Pollock, 25 Blatt; 11.-14. Aktennotizen; 11. "Bericht über die Verhandlungen zwischen Herrn Professor Baumgarten, Tenbruck und Habermas am 12.12.1956 im Institut für vergleichende Sozialwissenschaften in Stuttgart. Betreff: Professorenstudie" 13.13.1956 vermutlich 13.03.1956. Typoskript, 2 Blatt; 12. Gembardt, Ulrich: Aktennotiz zur Hochschuluntersuchung. 23.05.1955, Typoskript, 3 Blatt; 13. Gembardt, Ulrich: Bemerkungen zur Aktennotiz vom 23.05.1955, Typoskript, 2 Blatt; 14. "Aktennotiz über die Hochschul-Forschungsprojekte des Göttinger Soziologischen Seminars und des Frankfurter Institut für Sozialforschung, die deim Hauptausschuß der Deutschen Forschungsgemeinschaft am 1. August 1953 zur Finanzierung vorgelegt werden" 20.07.1953. Typoskript, 2 Blatt; 15.-18. Briefe; 15. Löwenthal, Leo: 1 Brief mit Unterschrift an MAx Horkheimer, New York, 20.01.1955, 3 Blatt; 16. Horkheimer, Max [?]: 1 Brief an Chauncy D. Harris, ohne Ort, Januar 1955; a) Typoskirpt, 1 Blatt; b) Typoskirpt mit handschriftlichen Korrekturen, 1 Blatt; c) Typoskirpt mit handschriftlichen Korrekturen, 1 Blatt; d) Typoskirpt, 1 Blatt; 17. Horkheimer, Max: Drei gleichlautende Briefe an die Rektoren der Universität Bonn, Heidelberg und Koel, ohne Ort, 15.11.1953; a) Typoskript, 6 Blatt; b) Typoskript mit eigenhändigen KOrrekturen, 3 Blatt; 18. Plessner, Helmuth: 1 Brief mit Unterschrift mit Beilage an Max Horkheimer, Göttingen 02.07.1953, 4 Blatt;

PREPARATION AND CHARACTERIZATION OF FAD DEPENDENT NADPH CYTOCHROME P-450 REDUCTASE (FLAVOPROTEINS, APOFLAVOPROTEIN)

NADPH cytochrome P-450 reductase releases FMN and FAD upon dilution into slightly acidic potassium bromide. The flavins are released with positive cooperativity. Dithiothreitol protects the FAD dependent cytochrome c reductase activity against inactivation by free radicals. Behavior in potassium bromide is sensitive to changes in the pH. High performance hydroxylapatite resolved the FAD dependent reductase from holoreductase. For 96% FAD dependent reductase, the overall yield was 12%.^ High FAD dependence was matched by a low FAD content, with FAD/FMN as low as 0.015. There were three molecules of FMN for every four molecules of reductase. The aporeductase had negligible activity towards cytochrome c, ferricyanide, menadione, dichlorophenolindophenol, nitro blue tetrazolium, oxygen and acetyl pyridine adenine dinucleotide phosphate. A four minute incubation in FAD reconstituted one half to all of the specific activity, per milligram protein, of untreated reductase, depending upon the substrate. After a two hour reconstitution, the reductase eluted from hydroxylapatite at the location of holoreductase. It had little flavin dependence, was equimolar in FMN and FAD, and had nearly the specific activity (per mole flavin) of untreated reductase.^ The lack of activity and the ability of FMN to also reconstitute suggest that the redox center of FAD is essential for catalysis, rather than for structure. Dependence upon FAD is consistent with existing hypotheses for the catalytic cycle of the reductase. ^