The technic of x-ray histochemistry applied to neurohistology

Zusammenfassung Demonstrationsvergleich röntgenmikroskopisch behandelter Zellen und Blutgefässe von Ratten sowie von menschlichem Gehirngewebe mit optischen Standardmethoden, wobei Gomoris Bleisulfidtechnik zur Bestimmung der Phosphataseenzymaktivität angewandt wurde. Die Brauchbarkeit der histochemischen Technik für die Röntgenologie wird diskutiert.

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This work formed part of the research submitted for a Master of Science degree at Dalhousie University. It was supported in part by MRC Grant No. MT-752 and carried out under the supervision and with the kind assistance of Prof. R. L. de C. H.Saunders.     

Nitrosamines and other carcinogens as agents of protein denaturation

Résumé Les auteurs montrent que les composés cancérogènes hydrosolubles, l'acide tannique, le phénol, la diéthyl-et diméthylnitrosamine, la thioacétamide, le carbamate d'éthyl et la thiourée sont des agents puissants de dénaturation de protéines. La précipitation produite par ces agents peut être inhibée, inversée ou accrue par divers réactifs de groupes sulfhydryles. Ces recoupements, ainsi que d'autres expériences sur l'effet de l'urée sur la précipitation par la diméthylnitrosamine, indiquent que le mécanisme de la formation des aggrégats moléculaires consiste dans l'établissement de ponts -S-S- intermoléculaires, probablement renforcés par des liaisons intermoléculaires d'hydrogène.

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This work was supported by USPHS Grant CY-4939 at the University of Florida, and by USPHS Grant C-5431 and a Grant-in-aid from the Greater New Orleans Cancer Association and the Cancer Society of Greater Baton Rouge, at Tulane University.

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Presented at the Fifty-second Annual Meeting of the American Association for Cancer Research, Atlantic City, N.J., April, 1961 (Abstr., Proc. Amer. Assoc. Cancer Research3, 206 (1961)).     

NLRX1 is a regulator of mitochondrial antiviral immunity

The RIG-like helicase (RLH) family of intracellular receptors detect viral nucleic acid and signal through the mitochondrial antiviral signalling adaptor MAVS (also known as Cardif, VISA and IPS-1) during a viral infection. MAVS activation leads to the rapid production of antiviral cytokines, including type 1 interferons. Although MAVS is vital to antiviral immunity, its regulation from within the mitochondria remains unknown. Here we describe human NLRX1, a highly conserved nucleotide-binding domain (NBD)- and leucine-rich-repeat (LRR)-containing family member (known as NLR) that localizes to the mitochondrial outer membrane and interacts with MAVS. Expression of NLRX1 results in the potent inhibition of RLH- and MAVS-mediated interferon-beta promoter activity and in the disruption of virus-induced RLH-MAVS interactions. Depletion of NLRX1 with small interference RNA promotes virus-induced type I interferon production and decreases viral replication. This work identifies NLRX1 as a check against mitochondrial antiviral responses and represents an intersection of three ancient cellular processes: NLR signalling, intracellular virus detection and the use of mitochondria as a platform for anti-pathogen signalling. This represents a conceptual advance, in that NLRX1 is a modulator of pathogen-associated molecular pattern receptors rather than a receptor, and identifies a key therapeutic target for enhancing antiviral responses.     

An inhibitor of Bcl-2 family proteins induces regression of solid tumours

Proteins in the Bcl-2 family are central regulators of programmed cell death, and members that inhibit apoptosis, such as Bcl-X(L) and Bcl-2, are overexpressed in many cancers and contribute to tumour initiation, progression and resistance to therapy. Bcl-X(L) expression correlates with chemo-resistance of tumour cell lines, and reductions in Bcl-2 increase sensitivity to anticancer drugs and enhance in vivo survival. The development of inhibitors of these proteins as potential anti-cancer therapeutics has been previously explored, but obtaining potent small-molecule inhibitors has proved difficult owing to the necessity of targeting a protein-protein interaction. Here, using nuclear magnetic resonance (NMR)-based screening, parallel synthesis and structure-based design, we have discovered ABT-737, a small-molecule inhibitor of the anti-apoptotic proteins Bcl-2, Bcl-X(L) and Bcl-w, with an affinity two to three orders of magnitude more potent than previously reported compounds. Mechanistic studies reveal that ABT-737 does not directly initiate the apoptotic process, but enhances the effects of death signals, displaying synergistic cytotoxicity with chemotherapeutics and radiation. ABT-737 exhibits single-agent-mechanism-based killing of cells from lymphoma and small-cell lung carcinoma lines, as well as primary patient-derived cells, and in animal models, ABT-737 improves survival, causes regression of established tumours, and produces cures in a high percentage of the mice.     

Trisomy of the T6 translocation chromosome in the mouse

Résumé En utilisant le chromosome T6 pour des expériences de transplantations dans la souris, nous avons trouvé des cellules contenant 41 chromosomes et le trisomique pour le chromosome T6.

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This work was supported by The Spastics Society, A.A.M. was in receipt of a grant from the Instituto de Alta Cultura, Portugal. Mr.L. Kelberman processed the photograph.