A novel monoquaternary neuromuscular blocking agent

Résumé Le M&B 15.944 (éthiodide dep-diméthylaminophényl heptyl cétone thiosémicarbazone) est un curarisant dont la brève durée d'action est comparable à celle de la succinylcholine chez divers espèces y compris le singe. Le méchanisme du blocage neuromusculaire provoqué par le M&B 15.944 est compétitif.     

The isolation and structure of 13,18-dehydroglaucarubinone,a new antineoplastic quassinoid fromSimarouba amara

Summary An investigation of the Guyana plantSimarouba amara Aubl. (Simaroubaceae) for antineoplastic quassinoids led to isolation and structural determination of the new quassinoids 2-acetylglaucarubine (1a) and 13,18-dehydroglaucarubinone (2). The previously known 2-acetylglaucarubinone (3a) and glaucarubinone (3b) were also obtained. The new quassinoid2 was found significantly to inhibit growth of the murine lymphocytic leukemia P388.Antineoplastic agents 59. For part 58 refer to M. T. Edgar, G.R. Pettit and T.H. Smith, J. org. Chem., in preparation.Acknowledgments. We wish to thank Mr B. Septe for providing the¹³C-NMR-data. Dr Jean H. Schmidt and Miss Linda M. Lange for assistance with biological studies.—G.R. Pettit is grateful to the National Cancer Institute (performed pursuant to contract No. N01-67048 with the Division of Cancer Treatment, NCI, National Institutes of Health, Dept. of Health, Education and Welfare), Public Health Services Research grant No. CA 16049-03 from the National Cancer Institute, the Fannie E. Rippel Foundation, Talley Industries, and the Phoenix Coca-Cola Bottling Co., for partial support of this investigation.     

On the mechanism of catalytic hydrogenation and dehydrogenation with rhodium

Zusammenfassung Mit Hilfe eines neuen Rhodiumpolyvinylalkohol-Katalysators wurde der Mechanismus katalytischer Hydrierungen und Dehydrierungen untersucht. Aus den mitgeteilten Versuchsergebnissen geht hervor, daß molekularer Wasserstoff durch Rhodiumionisiert wird, während mit Palladiumatomarer Wasserstoff gebildet wird. Bei der Untersuchung von Dehydrierungen wurde festgestellt, daß diese Reaktionen in Gegenwart von elementarem Schwefel beschleunigt werden. Der Schwefel wirkt entweder als Wasserstoffakzeptor oder nimmt an einer Komplexbildung teil.

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Contribution No. 57.     

The Lkb1 metabolic sensor maintains haematopoietic stem cell survival

Haematopoietic stem cells (HSCs) can convert between growth states that have marked differences in bioenergetic needs. Although often quiescent in adults, these cells become proliferative upon physiological demand. Balancing HSC energetics in response to nutrient availability and growth state is poorly understood, yet essential for the dynamism of the haematopoietic system. Here we show that the Lkb1 tumour suppressor is critical for the maintenance of energy homeostasis in haematopoietic cells. Lkb1 inactivation in adult mice causes loss of HSC quiescence followed by rapid depletion of all haematopoietic subpopulations. Lkb1-deficient bone marrow cells exhibit mitochondrial defects, alterations in lipid and nucleotide metabolism, and depletion of cellular ATP. The haematopoietic effects are largely independent of Lkb1 regulation of AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) signalling. Instead, these data define a central role for Lkb1 in restricting HSC entry into cell cycle and in broadly maintaining energy homeostasis in haematopoietic cells through a novel metabolic checkpoint.     

Calmodulin interacts with MLO protein to regulate defence against mildew in barley

In plants, defence against specific isolates of a pathogen can be triggered by the presence of a corresponding race-specific resistance gene, whereas resistance of a more broad-spectrum nature can result from recessive, presumably loss-of-regulatory-function, mutations. An example of the latter are mlo mutations in barley, which have been successful in agriculture for the control of powdery mildew fungus (Blumeria graminis f. sp. hordei; Bgh). MLO protein resides in the plasma membrane, has seven transmembrane domains, and is the prototype of a sequence-diversified family unique to plants, reminiscent of the seven-transmembrane receptors in fungi and animals. In animals, these are known as G-protein-coupled receptors and exist in three main families, lacking sequence similarity, that are thought to be an example of molecular convergence. MLO seems to function independently of heterotrimeric G proteins. We have identified a domain in MLO that mediates a Ca2+-dependent interaction with calmodulin in vitro. Loss of calmodulin binding halves the ability of MLO to negatively regulate defence against powdery mildew in vivo. We propose a sensor role for MLO in the modulation of defence reactions.     

The effects of nerve growth factor antiserum on ambystoma

Résumé Des injections d'un sérum spécifique contre le facteur de croissance nerveuse (anti-NGF) provoquent une réduction de la taille des ganglions rachidiens de la salamandreAmbystoma par suite de la réduction de la masse cellulaire du ganglion. Il y a aussi un plus grand nombre de «petites» cellules (d'un diamètre nucléaire de moins de 6,25 ) dans les ganglions des animaux utilisés.

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I should like to express my thanks to Dr.Isaac Schenkein for supplying the antiserum preparation, and to Mr.Edward Kalmar for technical assistance. This research was supported by a grant from the Rutgers University Research Council.     

The larval ring gland ofDrosophila melanogaster: A comparison of Ebony and Oregon strains by use of a qualitative protein stain

Résumé Le contenu protéique des cellules glandulaires circulaires des larves de 2 races deDrosophila melanogaster est examiné en détail. Les résultats de cette étude montrent que la production et l'activité hormonale de ces 2 races diffère.     

Identification of chicken lysozyme <Emphasis Type="Italic">g</Emphasis>2 and its expression in the intestine

Lysozyme is an important component of the innate immune system, protecting the gastrointestinal tract from infection. The aim of the present study was to determine if lysozyme is expressed in the chicken (Gallus gallus) intestine and to characterise the molecular forms expressed. Immunohistochemical staining localised lysozyme to epithelial cells of the villous epithelium along the length of the small intestine. There was no evidence for lysozyme expression in crypt epithelium and no evidence for Paneth cells. Immunoblots of chicken intestinal protein revealed three proteins: a 14-kDa band consistent with lysozyme c, and two additional bands of approximately 21 and 23 kDa, the latter consistent with lysozyme g. RT-PCR analyses confirmed that lysozyme c mRNA is expressed in 4-day, but not older chicken intestine and lysozyme g in 4- to 35-day chicken intestine. A novel chicken lysozyme g2 gene was identified by in silico analyses and mRNA for this lysozyme g2 was identified in the intestine from chickens of all ages. Chicken lysozyme g2 shows similarity with fish lysozyme g, including the absence of a signal peptide and cysteines involved in disulphide bond formation of the mammalian and bird lysozyme g proteins. Analyses using SecretomeP predict that chicken lysozyme g2 may be secreted by the non-classical secretory pathway. We conclude that lysozyme is expressed in the chicken small intestine by villous enterocytes. Lysozyme c, lysozyme g and g2 may fulfil complimentary roles in protecting the intestine.Received 4 August 2004; received after revision 1 September 2004; accepted 7 September 2004