The second messenger linking receptor activation to internal Ca release in liver

The increase in cytosolic [Ca2+] induced by Ca-mobilizing hormones in liver is mainly due to release of Ca from intracellular stores. For Ca to be released from internal sites a messenger must be formed at the plasma membrane which diffuses into the cytosol to signal Ca release from the intracellular organelles. One of the first actions of these hormones is to cause breakdown of the polyphosphoinositides to form soluble inositol phosphates. Some evidence for the idea that these substances could be the second messenger has been obtained in pancreatic acinar cells. Here we have found that hormone activation of hepatocytes causes rapid breakdown of phosphatidylinositol 4,5-bisphosphate [ PtdIns (4,5)P2] to form inositol trisphosphate ( InsP3 ). When applied to permeabilized hepatocytes, InsP3 releases Ca from non-mitochondrial ATP-dependent pools. This suggests that InsP3 could be the messenger linking Ca-mobilizing receptor activation to intracellular Ca release in liver.     

DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage

Chromosome 17 is unusual among the human chromosomes in many respects. It is the largest human autosome with orthology to only a single mouse chromosome, mapping entirely to the distal half of mouse chromosome 11. Chromosome 17 is rich in protein-coding genes, having the second highest gene density in the genome. It is also enriched in segmental duplications, ranking third in density among the autosomes. Here we report a finished sequence for human chromosome 17, as well as a structural comparison with the finished sequence for mouse chromosome 11, the first finished mouse chromosome. Comparison of the orthologous regions reveals striking differences. In contrast to the typical pattern seen in mammalian evolution, the human sequence has undergone extensive intrachromosomal rearrangement, whereas the mouse sequence has been remarkably stable. Moreover, although the human sequence has a high density of segmental duplication, the mouse sequence has a very low density. Notably, these segmental duplications correspond closely to the sites of structural rearrangement, demonstrating a link between duplication and rearrangement. Examination of the main classes of duplicated segments provides insight into the dynamics underlying expansion of chromosome-specific, low-copy repeats in the human genome.     

Suppression of star formation in early-type galaxies by feedback from supermassive black holes

Detailed high-resolution observations of the innermost regions of nearby galaxies have revealed the presence of supermassive black holes. These black holes may interact with their host galaxies by means of 'feedback' in the form of energy and material jets; this feedback affects the evolution of the host and gives rise to observed relations between the black hole and the host. Here we report observations of the ultraviolet emissions of massive early-type galaxies. We derive an empirical relation for a critical black-hole mass (as a function of velocity dispersion) above which the outflows from these black holes suppress star formation in their hosts by heating and expelling all available cold gas. Supermassive black holes are negligible in mass compared to their hosts but nevertheless seem to play a critical role in the star formation history of galaxies.     

High-power terahertz radiation from relativistic electrons

Terahertz (THz) radiation, which lies in the far-infrared region, is at the interface of electronics and photonics. Narrow-band THz radiation can be produced by free-electron lasers and fast diodes. Broadband THz radiation can be produced by thermal sources and, more recently, by table-top laser-driven sources and by short electron bunches in accelerators, but so far only with low power. Here we report calculations and measurements that confirm the production of high-power broadband THz radiation from subpicosecond electron bunches in an accelerator. The average power is nearly 20 watts, several orders of magnitude higher than any existing source, which could enable various new applications. In particular, many materials have distinct absorptive and dispersive properties in this spectral range, so that THz imaging could reveal interesting features. For example, it would be possible to image the distribution of specific proteins or water in tissue, or buried metal layers in semiconductors; the present source would allow full-field, real-time capture of such images. High peak and average power THz sources are also critical in driving new nonlinear phenomena and for pump-probe studies of dynamical properties of materials.     

A Cenozoic record of the equatorial Pacific carbonate compensation depth

Atmospheric carbon dioxide concentrations and climate are regulated on geological timescales by the balance between carbon input from volcanic and metamorphic outgassing and its removal by weathering feedbacks; these feedbacks involve the erosion of silicate rocks and organic-carbon-bearing rocks. The integrated effect of these processes is reflected in the calcium carbonate compensation depth, which is the oceanic depth at which calcium carbonate is dissolved. Here we present a carbonate accumulation record that covers the past 53 million years from a depth transect in the equatorial Pacific Ocean. The carbonate compensation depth tracks long-term ocean cooling, deepening from 3.0-3.5?kilometres during the early Cenozoic (approximately 55?million years ago) to 4.6 kilometres at present, consistent with an overall Cenozoic increase in weathering. We find large superimposed fluctuations in carbonate compensation depth during the middle and late Eocene. Using Earth system models, we identify changes in weathering and the mode of organic-carbon delivery as two key processes to explain these large-scale Eocene fluctuations of the carbonate compensation depth.     

A saturable receptor for 32P-inositol-1,4,5-triphosphate in hepatocytes and neutrophils

Several receptors for neurotransmitters, hormones and growth factors cause accelerated phosphodiesteratic breakdown of polyphosphoinositides when activated. One of the soluble products of this reaction, inositol-1,4,5-trisphosphate (Ins(1,4,5)P3) is thought to act as a second messenger signalling the release of Ca2+ from intracellular stores. In support of this hypothesis, several studies have shown that Ins(1,4,5)P3 releases sequestered Ca2+ from permeable cells and microsomes. On the basis of certain structural requirements for Ca2+-releasing activity by inositol phosphates, it has been postulated that Ins(1,4,5)P3 acts by binding to a specific intracellular receptor, probably on a component of the endoplasmic reticulum. Here we report that 32P-Ins(1,4,5)P3 binds to a specific saturable site in permeabilized guinea pig hepatocytes and rabbit neutrophils, and that the properties of this binding site suggest that it is the physiological receptor for Ins(1,4,5)P3.     

Synthesis and reactions of a proposed DDT metabolite, 2,2-bis(p-chlorophenyl)acetaldehyde

Zusammenfassung Es wird eine Methode beschrieben, nach der authentischer 2, 2-bis(p-chlorphenyl)acetaldehyd erhalten wird. Die Charakterisierung dieses Aldehyds hat gezeigt, dass die in der Literatur bisher erschienen Angaben unrichtig sind. Der Aldehyd geht unter milden oxydativen Bedingungen unter Deformylierung in 4, 4-Dichlorbenzophenon Über. Mögliche biologische Bedeutung dieser Reaktionen werden diskutiert.