Structural changes in glycogen phosphorylase induced by phosphorylation

A comparison of the refined crystal structures of dimeric glycogen phosphorylase b and a reveals structural changes that represent the first step in the activation of the enzyme. On phosphorylation of serine-14, the N-terminus of each subunit assumes an ordered helical conformation and binds to the surface of the dimer. The consequent structural changes at the N- and C-terminal regions lead to strengthened interactions between subunits and alter the binding sites for allosteric effectors and substrates.     

Sex chromosome aberrations involving loss and translocation of tumor-inducing loci inXiphophorus

Summary Karyotypic changes involving a deletion and a translocation of certain sex-linked tumor-inducing loci of the platyfish,Platypoecilus (Xiphophorus) maculatus, have been investigated. The effects of these chromosome aberrations on tumor formation and viability of the fish are discussed.Supported by DFG through SFB 103 (Zellenergetik und Zelldifferenzierung, Marburg). We thank Käte Klinke for providing fish stocks.     

Amino acids as stimulating agents of DNA replication in melanomas II. Stimulation in in-situ melanomas

Zusammenfassung Nach abrupter überführung von Zahnkarpfen aus Süsswasser in verdünntes Meerwasser schwingt sich der Pool der sogenannten freien Aminosäuren von einem ursprünglichen auf einen neuen erhöhten stationären Zustand ein. Ein ganz entsprechendes Zeitverhalten hat der H³-Thymidin-Markierungsindex (Anzahl markierter Kerne/Gesamtkernzahl) in Melanomen von Bastarden, deren Farbzellen genetisch total dereprimiert sind.     

Comparison of the in vitro effects of colchicine and its derivative colchiceine on chondrocyte morphology and function

Summary Colchiceine is a colchicine-metabolite which has been reported to inhibit axonal transport although not binding to brain tubulin. In the present study, colchiceine was shown not to depolymerize cytoplasmic microtubules, nor to mimic other effects of colchicine on the ultrastructure of cultured chondrocytes. In addition, the synthesis of proteoglycans was inhibited by colchicine but slightly stimulated by colchiceine. These results support the idea that the disturbances in cultured chondrocytes caused by colchicine are specifically related to a loss of cytoplasmic microtubules.This work was supported by grants from the Swedish Medical Research Council (proj. No. 12X-03355), the King Gustaf V 80th Birthday Fund, the Swedish Society of Medical Sciences, and from the funds of Karolinska Institutet.     

DNA-mediated transformation in the platyfish-swordtail melanoma system

A genetic marker, the tumor geneTu, which causes the formation of abnormal melanophores, the T-melanophores, in the skin of Xiphophorine fish has been transferred by donor DNA from aTu genotype to recipient embryos lackingTu. Abnormal melanophores which are identical to the T-melanophores of the donor genotype occurred only in recipients treated withTu-DNA and not in those treated withTu-free control DNA.     

A variant associated with nicotine dependence, lung cancer and peripheral arterial disease

Smoking is a leading cause of preventable death, causing about 5 million premature deaths worldwide each year. Evidence for genetic influence on smoking behaviour and nicotine dependence (ND) has prompted a search for susceptibility genes. Furthermore, assessing the impact of sequence variants on smoking-related diseases is important to public health. Smoking is the major risk factor for lung cancer (LC) and is one of the main risk factors for peripheral arterial disease (PAD). Here we identify a common variant in the nicotinic acetylcholine receptor gene cluster on chromosome 15q24 with an effect on smoking quantity, ND and the risk of two smoking-related diseases in populations of European descent. The variant has an effect on the number of cigarettes smoked per day in our sample of smokers. The same variant was associated with ND in a previous genome-wide association study that used low-quantity smokers as controls, and with a similar approach we observe a highly significant association with ND. A comparison of cases of LC and PAD with population controls each showed that the variant confers risk of LC and PAD. The findings provide a case study of a gene-environment interaction, highlighting the role of nicotine addiction in the pathology of other serious diseases.