Engraftment of connexin 43-expressing cells prevents post-infarct arrhythmia

Ventricular tachyarrhythmias are the main cause of sudden death in patients after myocardial infarction. Here we show that transplantation of embryonic cardiomyocytes (eCMs) in myocardial infarcts protects against the induction of ventricular tachycardia (VT) in mice. Engraftment of eCMs, but not skeletal myoblasts (SMs), bone marrow cells or cardiac myofibroblasts, markedly decreased the incidence of VT induced by in vivo pacing. eCM engraftment results in improved electrical coupling between the surrounding myocardium and the infarct region, and Ca2+ signals from engrafted eCMs expressing a genetically encoded Ca2+ indicator could be entrained during sinoatrial cardiac activation in vivo. eCM grafts also increased conduction velocity and decreased the incidence of conduction block within the infarct. VT protection is critically dependent on expression of the gap-junction protein connexin 43 (Cx43; also known as Gja1): SMs genetically engineered to express Cx43 conferred a similar protection to that of eCMs against induced VT. Thus, engraftment of Cx43-expressing myocytes has the potential to reduce life-threatening post-infarct arrhythmias through the augmentation of intercellular coupling, suggesting autologous strategies for cardiac cell-based therapy.     

1A6/DRIM,the human UTP20 functions in 28S and 5.8S rRNA processing

1A6/DRIM has been identified as UTP20, a small subunit processome component, functioning in 18S rRNA processing. In the present study, the maturation of 28S rRNA and 5.8S rRNA was inhibited when 1A6/DRIM was silenced in HeLa cells; and coin-cidently, an accumulation of 32S rRNA precursor was observed. Immunoprecipitation was performed with the anti-1A6/DRIM antibody, followed by Northern blot with the ITS2 probe. The results showed that 1A6/DRIM was associated with both 32S and 12S rRNA precursors in vivo. The expression profile of 1A6/DRIM during rRNA processing was investigated by sucrose density gradient fractionation in combination with Western blot analysis. The results demonstrated that 1A6/DRIM was involved in the pre-60S particles in addition to the pre-40S particles and co-sediment with the 32S and 12S rRNA precursors in the nucleolus. Furthermore, the interaction of U8 snoRNA with 1A6/DRIM was revealed by immunoprecipitation. These results demonstrated that 1A6/DRIM interacted with both 32S rRNA and U8 snoRNA, being involved in 28S rRNA and 5.8S rRNA processing.     

Some difficulties of ecological thinking,considered from a critical systems perspective: A plea for critical holism

We probably have simplified matters too much. We tend to talk about systems thinking and practice as if we knew what they are. The fashionable call for “holistic” or “systems” thinking in ecological issues provides a major example. This much is certain: the quest for comprehensiveness, although it represents an epistemologically necessary idea, is not realizable. If we assume that it is realizable, the critical idea underlying the quest will be perverted into its opposite, i.e., into a false pretension to superior knowledge and understanding—a danger of which the environmental movement does not always appear to be sufficiently aware. My question, therefore, is this: How can we deal critically with the fact that our thinking, and hence our knowledge, designs, and actions, cannot possibly be comprehensive, in the sense that we never “comprehend” all that ought to be understood before we pass to judgment and action? What consequences does this fact imply for a critical systems approach to ecological concerns and, ultimately, for our concepts of rationality in general?     

An improved method for the collection of large numbers of inseminated eggs ofDrosophila melanogaster

Zusammenfassung Es wird eine verbesserte Methode beschrieben, mit der innerhalb einer Sammelperiode von 3 min etwa 50-100 frisch besamte Eier vonDrosophila melanogaster gewonnen werden können. Verglichen mit den bisher üblichen Sammelperioden von 10, 30 oder mehr min erhält man wesentlich stadienhomogenere Gelege. Eine weitere Verkürzung der Sammelperiode unter 3 min ist wegen der stark abnehmenden Anzahl Eier je Gelege nicht möglich. Vorausgesetzt, dass alle Störungen der Fliegen durch Erschütterungen, Licht, Temperaturschwankungen usw ausgeschaltet werden, können z.B. für strahlenbiologische Experimente zahlreiche 3-min-Gelege im Laufe von 6 oder mehr Stunden gewonnen werden.

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Work supported by Schweizerischer Nationalfonds zur Förderung der wissenschaftlichen Forschung and Jubiläumsfond 1930 der ETH.     

中锰钢奥氏体逆相变的多相场模拟

Medium-Mn steels have attracted immense attention for automotive applications owing to their outstanding combination of high strength and superior ductility. This steel class is generally characterized by an ultrafine-grained duplex microstructure consisting of ferrite and a large amount of austenite. Such a unique microstructure is processed by intercritical annealing, where austenite reversion occurs in a fine martensitic matrix. In the present study, austenite reversion in a medium-Mn alloy was simulated by the multiphase-field approach using the commercial software MICRESS? coupled with the thermodynamic database TCFE8 and the kinetic database MOBFE2. In particular, a faceted anisotropy model was incorporated to replicate the lamellar morphology of reversed austenite. The simulated microstructural morphology and phase transformation kinetics (indicated by the amount of phase) concurred well with experimental observations by scanning electron microscopy and in situ synchrotron high-energy X-ray diffraction, respectively.     

Anthropogenic and natural acidification in terrestrial ecosystems

Conclusions The total proton load found in these ecosystems exceeds by far the known rates of buffering in soils by silicate weathering and release of basic cations (see above).Under the present proton load most forest soils will therefore acidify and besides losses of nutrients the occurrence of possible toxic ions in the soil unavoidable (Al-buffer range)^{20, 21}.The proportion of the total proton load of the soil that is represented by the internal production emphasizes the importance of acid deposition as main cause of soil acidification and destabilization of forest ecosystems under Central European conditions.     

Genetic variation in DLG5 is associated with inflammatory bowel disease

Crohn disease and ulcerative colitis are two subphenotypes of inflammatory bowel disease (IBD), a complex disorder resulting from gene-environment interaction. We refined our previously defined linkage region for IBD on chromosome 10q23 and used positional cloning to identify genetic variants in DLG5 associated with IBD. DLG5 encodes a scaffolding protein involved in the maintenance of epithelial integrity. We identified two distinct haplotypes with a replicable distortion in transmission (P = 0.000023 and P = 0.004 for association with IBD, P = 0.00012 and P = 0.04 for association with Crohn disease). One of the risk-associated DLG5 haplotypes is distinguished from the common haplotype by a nonsynonymous single-nucleotide polymorphism 113G-->A, resulting in the amino acid substitution R30Q in the DUF622 domain of DLG5. This mutation probably impedes scaffolding of DLG5. We stratified the study sample according to the presence of risk-associated CARD15 variants to study potential gene-gene interaction. We found a significant difference in association of the 113A DLG5 variant with Crohn disease in affected individuals carrying the risk-associated CARD15 alleles versus those carrying non-risk-associated CARD15 alleles. This is suggestive of a complex pattern of gene-gene interaction between DLG5 and CARD15, reflecting the complex nature of polygenic diseases. Further functional studies will evaluate the biological significance of DLG5 variants.     

Mutations in cadherin 23 affect tip links in zebrafish sensory hair cells

Hair cells have highly organized bundles of apical projections, or stereocilia, that are deflected by sound and movement. Displacement of stereocilia stretches linkages at the tips of stereocilia that are thought to gate mechanosensory channels. To identify the molecular machinery that mediates mechanotransduction in hair cells, zebrafish mutants were identified with defects in balance and hearing. In sputnik mutants, stereociliary bundles are splayed to various degrees, with individuals displaying reduced or absent mechanotransduction. Here we show that the defects in sputnik mutants are caused by mutations in cadherin 23 (cdh23). Mutations in Cdh23 also cause deafness and vestibular defects in mice and humans, and the protein is present in hair bundles. We show that zebrafish Cdh23 protein is concentrated near the tips of hair bundles, and that tip links are absent in homozygous sputnik(tc317e) larvae. Moreover, tip links are absent in larvae carrying weak alleles of cdh23 that affect mechanotransduction but not hair bundle integrity. We conclude that Cdh23 is an essential tip link component required for hair-cell mechanotransduction.