The postnatal development of hormone sensitive lipase in brown and white adipose tissue of the rat

Zusammenfassung Die Aktivität hormonsensitiver Lipasen im weissen und braunen Fettgewebe der Ratte steigt zwischen dem 10. und 18. Tag nach der Geburt. Corticosteronzufuhr verursacht bei 10tägigen Ratten einen Aktivitätsanstieg. Adrenalin und Noradrenalin haben im braunen Fettgewebe keinen Effekt.     

Measurement of collateral flow in experimental coronary occlusion

Zusammenfassung Es wird ein Verfahren zur autoradiographischen Darstellung der intramyocardialen Durchblutungsverteilung nach experimenteller Coronarocclusion angegeben. Im Versorgungsbereich akut verschlossener Coronararterien wird eine inhomogene Reduktion der Durchblutung beobachtet, wobei die Innenschichten regelmässig stärker als die subepicardialen Myocardanteile betroffen sind.     

Mutation of Vps54 causes motor neuron disease and defective spermiogenesis in the wobbler mouse

Vacuolar-vesicular protein sorting (Vps) factors are involved in vesicular trafficking in eukaryotic cells. We identified the missense mutation L967Q in Vps54 in the wobbler mouse, an animal model of amyotrophic lateral sclerosis, and also characterized a lethal allele, Vps54(beta-geo). Motoneuron survival and spermiogenesis are severely compromised in the wobbler mouse, indicating that Vps54 has an essential role in these processes.     

The role of kinesin, dynein and microtubules in pancreatic secretion

The regulated secretion of pancreatic zymogens depends on a functional cytoskeleton and intracellular vesicle transport. To study the dynamics of tubulin and its motor proteins dynein and kinesin during secretion in pancreatic acinar cells, we infused rats with 0.1 μg/kg/h caerulein. Electron and fluorescence microscopy detected neither dynein nor kinesin at the apical secretory pole, nor on the surface of mature zymogen granules. After 30 min of secretagogue stimulation, kinesin and the Golgi marker protein 58 K were reallocated towards the apical plasma membrane and association of kinesin with tubulin was enhanced. Disruption of acinar cell microtubules had no effect on initial caerulein-induced amylase release but completely blocked secretion during a second stimulus. Our results suggest that mature zymogen granule exocytosis is independent of intact microtubules, kinesin and dynein. However, microtubule-dependent mechanisms seem to be important for the replenishment of secretory vesicles by redistribution of Golgi elements towards the apical cell pole. J. Schnekenburger and I.-A. Weber have contributed equally to this work.     

Transformation from committed progenitor to leukaemia stem cell initiated by MLL-AF9

Leukaemias and other cancers possess a rare population of cells capable of the limitless self-renewal necessary for cancer initiation and maintenance. Eradication of these cancer stem cells is probably a critical part of any successful anti-cancer therapy, and may explain why conventional cancer therapies are often effective in reducing tumour burden, but are only rarely curative. Given that both normal and cancer stem cells are capable of self-renewal, the extent to which cancer stem cells resemble normal tissue stem cells is a critical issue if targeted therapies are to be developed. However, it remains unclear whether cancer stem cells must be phenotypically similar to normal tissue stem cells or whether they can retain the identity of committed progenitors. Here we show that leukaemia stem cells (LSC) can maintain the global identity of the progenitor from which they arose while activating a limited stem-cell- or self-renewal-associated programme. We isolated LSC from leukaemias initiated in committed granulocyte macrophage progenitors through introduction of the MLL-AF9 fusion protein encoded by the t(9;11)(p22;q23). The LSC were capable of transferring leukaemia to secondary recipient mice when only four cells were transferred, and possessed an immunophenotype and global gene expression profile very similar to that of normal granulocyte macrophage progenitors. However, a subset of genes highly expressed in normal haematopoietic stem cells was re-activated in LSC. LSC can thus be generated from committed progenitors without widespread reprogramming of gene expression, and a leukaemia self-renewal-associated signature is activated in the process. Our findings define progression from normal progenitor to cancer stem cell, and suggest that targeting a self-renewal programme expressed in an abnormal context may be possible.     

The Pendulum Swings Again: A Mathematical Reassessment of Galileo's Experiments with Inclined Planes

 After over 300 years of scrutiny, the subject of Galileo continues to be pursued with unabating intensity. Dava Sobel's Galileo's Daughter points to the popular interest in the man and his legacy. The Catholic Church, understandably interested in dispelling the notion that its censure of Galileo centuries ago is proof positive that religious faith and science as well as ecclesiastical authority and free pursuit of scholarship are irreconcilable, continues to offer explanations. New books, articles and conferences probe both in breadth and in depth the magnetic field charged by Galileo, science, and the Church. Galileo's analysis of the physics of motion has also received considerable attention. In particular, a great deal has been written during the past thirty years about the structure and objectives of three experiments with inclined planes. Galileo had carried them out in Padua and recorded them in his working papers. The assessments of the three experiments differ widely in points of detail, but all regard them as sophisticated, ingenious, and remarkable. This article presents a new critical study of these experiments. Its conclusion is that one of the experiments is indeed a success, but that the other two fail and are abandoned because Galileo did not have a firm enough grip on the underlying physical principles and mathematical relationships.     

Claudin-1 is a hepatitis C virus co-receptor required for a late step in entry

Hepatitis C virus (HCV) is a leading cause of cirrhosis and liver cancer worldwide. A better understanding of the viral life cycle, including the mechanisms of entry into host cells, is needed to identify novel therapeutic targets. Although HCV entry requires the CD81 co-receptor, and other host molecules have been implicated, at least one factor critical to this process remains unknown (reviewed in refs 1-3). Using an iterative expression cloning approach we identified claudin-1 (CLDN1), a tight junction component that is highly expressed in the liver, as essential for HCV entry. CLDN1 is required for HCV infection of human hepatoma cell lines and is the first factor to confer susceptibility to HCV when ectopically expressed in non-hepatic cells. Discrete residues within the first extracellular loop (EL1) of CLDN1, but not protein interaction motifs in intracellular domains, are critical for HCV entry. Moreover, antibodies directed against an epitope inserted in the CLDN1 EL1 block HCV infection. The kinetics of this inhibition indicate that CLDN1 acts late in the entry process, after virus binding and interaction with the HCV co-receptor CD81. With CLDN1 we have identified a novel key factor for HCV entry and a new target for antiviral drug development.