Lucibufagins,IV. New defensive steroids and a pterin from the firefly,Photinus pyralis (coleoptera: Lampyridae)

Summary Two new defensive steroids (lucibufagins6 and7) and a fluorescent pterin (8) have been isolated and characterized from the fireflyPhotinus pyralis.Acknowledgment. We are grateful to the Fonds National Suisse de la Recherche Scientifique (bourse de relève to M.G.). Partial support of this work by the NIH (grants No. AI 12020 and AI 02908), the NSF (grant No. PCM-77-25807), and the American Heart Association is acknowledged with pleasure. Paper No. 66 of the series Defense Mechanism of Arthropods.     

Effect of a potent hypolipemic agent on glycogen metabolism

Resumen Mediante la incubación de hemidiafragmas de ratón, se estudió el efecto de un potente hipolipemiante sobre la síntesis de glucógeno in vitro. Este compuesto. 3-PT, produjo un franco incremento de la síntesis de glucógeno, comparable al obtenido con 1 mU de insulina.

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Thanks are due to Dr.Echave Llanos for the kind provision of mice.

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This work was partially supported with funds provided by Gador Argentina S.A.     

Development of adenocarcinomas after transplantation of rat glandular stomachs treated in vitro with N-methyl-N′-nitro-N-nitrosoguanidine (MNNG)

Cellular and Molecular Life Sciences - Glandular stomachs of fetal and newborn Wistar rats were transplanted s.c. after treatment in vitro with N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) at...     

Human heart disease: lessons from human pluripotent stem cell-derived cardiomyocytes

Technical advances in generating and phenotyping cardiomyocytes from human pluripotent stem cells (hPSC-CMs) are now driving their wider acceptance as in vitro models to understand human heart disease and discover therapeutic targets that may lead to new compounds for clinical use. Current literature clearly shows that hPSC-CMs recapitulate many molecular, cellular, and functional aspects of human heart pathophysiology and their responses to cardioactive drugs. Here, we provide a comprehensive overview of hPSC-CMs models that have been described to date and highlight their most recent and remarkable contributions to research on cardiovascular diseases and disorders with cardiac traits. We conclude discussing immediate challenges, limitations, and emerging solutions.     

Engineering a mouse balancer chromosome.

Balancer chromosomes are genetic reagents that are used in Drosophila melanogaster for stock maintenance and mutagenesis screens. Despite their utility, balancer chromosomes are rarely used in mice because they are difficult to generate using conventional methods. Here we describe the engineering of a mouse balancer chromosome with the Cre-loxP recombination system. The chromosome features a 24-centiMorgan (cM) inversion between Trp53 (also known as p53) and Wnt3 on mouse chromosome 11 that is recessive lethal and dominantly marked with a K14-Agouti transgene. When allelic to a wild-type chromosome, the inversion suppresses crossing over in the inversion interval, accompanied by elevated recombination in the flanking regions. The inversion functions as a balancer chromosome because it can be used to maintain a lethal mutation in the inversion interval as a self-sustaining trans-heterozygous stock. This strategy can be used to generate similar genetic reagents throughout the mouse genome. Engineering of visibly marked inversions and deficiencies is an important step toward functional analyses of the mouse genome and will facilitate large-scale mutagenesis programs.     

Evaluation of the hepatotoxicological effects of a drug in an in vivo/in vitro model.

Both in vivo and in vitro models have certain disadvantages for the study of the chronic hepatotoxicity of drugs. The aim of this work was to evaluate a new approach based on an in vivo/in vitro model. After chronic in vivo treatment of rats with Vincamine and Vindeburnol (an eburnamenine derivative which exhibits hepatotoxic properties in man) liver cells were isolated, and functional and metabolic disorders (metabolic utilization of fructose and protein biosynthesis) were studied to determine injury. The results showed no modification of blood parameters, but a direct relationship between the dose of Vindeburnol administered in vivo and the metabolic disorders observed in vitro, evidencing the high sensitivity and reliability of this model.     

Conditional and joint multiple-SNP analysis of GWAS summary statistics identifies additional variants influencing complex traits

We present an approximate conditional and joint association analysis that can use summary-level statistics from a meta-analysis of genome-wide association studies (GWAS) and estimated linkage disequilibrium (LD) from a reference sample with individual-level genotype data. Using this method, we analyzed meta-analysis summary data from the GIANT Consortium for height and body mass index (BMI), with the LD structure estimated from genotype data in two independent cohorts. We identified 36 loci with multiple associated variants for height (38 leading and 49 additional SNPs, 87 in total) via a genome-wide SNP selection procedure. The 49 new SNPs explain approximately 1.3% of variance, nearly doubling the heritability explained at the 36 loci. We did not find any locus showing multiple associated SNPs for BMI. The method we present is computationally fast and is also applicable to case-control data, which we demonstrate in an example from meta-analysis of type 2 diabetes by the DIAGRAM Consortium.