Dual modes of the carbon cycle since the Last Glacial Maximum

The most conspicuous feature of the record of past climate contained in polar ice is the rapid warming which occurs after long intervals of gradual cooling. During the last four transitions from glacial to interglacial conditions, over which such abrupt warmings occur, ice records indicate that the CO2 concentration of the atmosphere increased by roughly 80 to 100 parts per million by volume. But the causes of the atmospheric CO2 concentration increases are unclear. Here we present the stable-carbon-isotope composition (delta 13 CO2) of CO2 extracted from air trapped in ice at Taylor Dome, Antarctica, from the Last Glacial Maximum to the onset of Holocene times. The global carbon cycle is shown to have operated in two distinct primary modes on the timescale of thousands of years, one when climate was changing relatively slowly and another when warming was rapid, each with a characteristic average stable-carbon-isotope composition of the net CO2 exchanged by the atmosphere with the land and oceans. delta 13 CO2 increased between 16.5 and 9 thousand years ago by slightly more than would be estimated to be caused by the physical effects of a 5 degrees C rise in global average sea surface temperature driving a CO2 efflux from the ocean, but our data do not allow specific causes to be constrained.     

Mei-P26 regulates microRNAs and cell growth in the Drosophila ovarian stem cell lineage

Drosophila neuroblasts and ovarian stem cells are well characterized models for stem cell biology. In both cell types, one daughter cell self-renews continuously while the other undergoes a limited number of divisions, stops to proliferate mitotically and differentiates. Whereas neuroblasts segregate the Trim-NHL (tripartite motif and Ncl-1, HT2A and Lin-41 domain)-containing protein Brain tumour (Brat) into one of the two daughter cells, ovarian stem cells are regulated by an extracellular signal from the surrounding stem cell niche. After division, one daughter cell looses niche contact. It undergoes 4 transit-amplifying divisions to form a cyst of 16 interconnected cells that reduce their rate of growth and stop to proliferate mitotically. Here we show that the Trim-NHL protein Mei-P26 (refs 7, 8) restricts growth and proliferation in the ovarian stem cell lineage. Mei-P26 expression is low in stem cells but is strongly induced in 16-cell cysts. In mei-P26 mutants, transit-amplifying cells are larger and proliferate indefinitely leading to the formation of an ovarian tumour. Like brat, mei-P26 regulates nucleolar size and can induce differentiation in Drosophila neuroblasts, suggesting that these genes act through the same pathway. We identify Argonaute-1, a component of the RISC complex, as a common binding partner of Brat and Mei-P26, and show that Mei-P26 acts by inhibiting the microRNA pathway. Mei-P26 and Brat have a similar domain composition that is also found in other tumour suppressors and might be a defining property of a new family of microRNA regulators that act specifically in stem cell lineages.     

Arc-parallel flow in the mantle wedge beneath Costa Rica and Nicaragua

Resolving flow geometry in the mantle wedge is central to understanding the thermal and chemical structure of subduction zones, subducting plate dehydration, and melting that leads to arc volcanism, which can threaten large populations and alter climate through gas and particle emission. Here we show that isotope geochemistry and seismic velocity anisotropy provide strong evidence for trench-parallel flow in the mantle wedge beneath Costa Rica and Nicaragua. This finding contradicts classical models, which predict trench-normal flow owing to the overlying wedge mantle being dragged downwards by the subducting plate. The isotopic signature of central Costa Rican volcanic rocks is not consistent with its derivation from the mantle wedge or eroded fore-arc complexes but instead from seamounts of the Galapagos hotspot track on the subducting Cocos plate. This isotopic signature decreases continuously from central Costa Rica to northwestern Nicaragua. As the age of the isotopic signature beneath Costa Rica can be constrained and its transport distance is known, minimum northwestward flow rates can be estimated (63-190 mm yr(-1)) and are comparable to the magnitude of subducting Cocos plate motion (approximately 85 mm yr(-1)). Trench-parallel flow needs to be taken into account in models evaluating thermal and chemical structure and melt generation in subduction zones.     

Effects of angiotensin II and of an angiotensin II receptor antagonist on Simian virus 40-induced tumor growth in vivo

Summary The effects of angiotensin II and of the competitive angiotensin II receptor antagonist saralasin on in vivo tumor growth were investigated in hamsters. Angiotensin II strongly inhibited tumor growth while saralasin stimulated it, though the high dose used had partial agonistic angiotensin II-like actions. Lower doses of saralasin were without significant effect on tumor weights.Acknowledgments. These studies were supported by the Deutsche Forschungsgemeinschaft (DFG) within the SFB 90 Cardiovaskuläres System. Saralasin was a gift from Dr A.W. Castellion, Norwich Pharmacal Company, USA. We thank S. Thiele, P. Baumgärtl and D. Kurz for excellent technical assistance.     

Inhibition of respiratory oxidation of reduced sulfur compounds by intact cells ofThiobacillus denitrificans (strain RT) grown on thiosulfate

Thiobacillus denitrificans strain RT, an obligate sulfur-oxidizing chemolithoautotroph, was grown under microaerophilic conditions with thiosulfate as the only energy source. The rates of tetrathionate, thiosulfate, elemental sulfur (S^o) and sulfite oxidation were measured respirometrically with an oxygen electrode, using actively growing cells. Cells oxidized thiosulfate, elemental sulfur (S^o) and sulfite, but not tetrathionate. The thiosulfateoxidizing activity and elemental sulfur-oxidizing activity (SOA) were almost totally inhibited by 50 M myxothiazol (>80%), an inhibitor of the quinone-cytochrome b region, and by 10 M of the uncoupler carbonyl cyanide m-chlorophenylhydrazone (CCCP) (>82%). Sulfite-oxidizing activity was also significantly inhibited (>60%) by 50 M myxothiazol and 10 M CCCP. 1 mM KCN totally inhibited (>90%) all respiratory activities. This study confirms that a sulfur-oxidizing activity appears during microaerophilic growth ofThiobacillus denitrificans strain RT on thiosulfate. The SOA is linked to the respiratory chain, probably releasing electrons in the quinone-cytochrome b region.To whom correspondence should be addressed. Submitted by R. Bachofen.     

The influence of GABA on discharges of cortical epileptogenic focus

Summary GABA, when applied locally, acted similarly on both primary and mirror cortical focus: the negative component of the spike discharge was suppressed or inverted in polarity, whereas the late slow negative wave was strongly potentiated. Recordings from deep cortical layers suggested a different origin of these 2 surface-negative components of focal discharges.     

Thromboxane synthase mutations in an increased bone density disorder (Ghosal syndrome)

Studying consanguineous families with Ghosal hematodiaphyseal dysplasia syndrome (GHDD), a disorder of increased bone density, we identified mutations in TBXAS1, which encodes thromboxane synthase (TXAS). TXAS, an enzyme of the arachidonic acid cascade, produces thromboxane A(2) (TXA(2)). Platelets from subjects with GHDD showed a specific deficit in arachidonic acid-produced aggregation. We also found that TXAS and TXA(2) modulated expression of TNFSF11 and TNFRSF11B (encoding RANKL and osteoprotegerin (OPG), respectively) in primary cultured osteoblasts.     

Finding the mid-path

Computers have changed nearly every aspect of life in this world. Invented roughly fifty years ago, they now form the infrastructure on which government, business, and global communications rest. As our reliance on computers increases, so does the number and complexity of the applications and the number and quality of trained professionals that will be needed to support further progress. The United States already faces personnel shortages in some computer-related jobs, including university teaching. In the face of this evident and increasing need, we must think clearly about out expectations for computing professionals of all sorts and the way they are trained. In the forty years that I have been in the field, the focus in industry has changed from programming to software development. A gulf is growing between the skills that students build at a university and the needs of industry. This paper examines the nature and extent of the problem and suggests a variety of ways to address it.     

Binding of disease-associated prion protein to plasminogen

Transmissible spongiform encephalopathies are associated with accumulation of PrP(Sc), a conformer of a cellular protein called PrP(C). PrP(Sc) is thought to replicate by imparting its conformation onto PrP(C) (ref. 1), yet conformational discrimination between PrP(C) and PrP(Sc) has remained elusive. Because deposition of PrP(Sc) alone is not enough to cause neuropathology, PrP(Sc) probably damages the brain by interacting with other cellular constituents. Here we find activities in human and mouse blood which bind PrP(Sc) and prion infectivity, but not PrP(C). We identify plasminogen, a pro-protease implicated in neuronal excitotoxicity, as a PrP(Sc)-binding protein. Binding is abolished if the conformation of PrP(Sc) is disrupted by 6M urea or guanidine. The isolated lysine binding site 1 of plasminogen (kringles I-III) retains this binding activity, and binding can be competed for with lysine. Therefore, plasminogen represents the first endogenous factor discriminating between normal and pathological prion protein. This unexpected property may be exploited for diagnostic purposes.