Vasorelaxant properties of the endothelium-derived relaxing factor more closely resemble S-nitrosocysteine than nitric oxide

Studies of cultured bovine aortic endothelial cells using quantitative chemiluminescence techniques have shown that the amount of nitric oxide released under basal conditions, or in response to either bradykinin or the calcium ionophore A23187 is insufficient to account for the vasorelaxant activities of the endothelium-derived relaxing factor (EDRF) derived from the same source. This observation contradicts previous suggestions that nitric oxide and EDRF are the same compound, but may be explained if EDRF is a compound that contains nitric oxide within its structure but is a much more potent vasodilator than nitric oxide. Such a molecule could be one of several nitrosothiols which may yield nitric oxide after a one-electron reduction. The present experiments were carried out to test the possibility that the biological activities of the endothelium-derived relaxing factor might more closely resemble those of one of these compounds, S-nitrosocysteine, than nitric oxide. Nitric oxide release from cultured bovine aortic endothelial cells was detected by chemiluminescence and bioassay experiments compared the vasodilator potencies of nitric oxide, S-nitrosocysteine, and EDRF. The results suggest that EDRF is much more likely to be a nitrosylated compound such as a nitrosothiol than authentic nitric oxide.     

A bayesian decision approach to model monitoring and cusums

Cumulative Sum techniques are widely used in quality control and model monitoring. A single-sided cusum may be regarded essentially as a sequence of sequential tests which, in many cases, such as those for the Exponential Family, is equivalent to a Sequence of Sequential Probability Ratio Tests. The relationship between cusums and Bayesian decisions is difficult to establish using conventional methods. An alternative approach is proposed which not only reveals a relation but also offers a very simple formulation of the decision process involved in model monitoring. This is first illustrated for a Normal mean and then extended to other important practical cases including Dynamic Models. For V-mask cusum graphs a particular feature is the interpretation of the distance of the V vertex from the latest plotted point in terms of the prior precision as measured in ‘equivalent’ observations.     

Evolutionary implications of ascorbic acid production in the Australian lungfish

Summary It is shown that the Australian lungfish (Neoceratodus forsteri) synthesizes ascorbic acid in its kidney, suggesting that ascorbic acid synthesis started before the origin of the tetrapods.Acknowledgments. We would like to thank Dr G.C. Grigg, University of Sydney, Mr R. B. Humphries, Dr P.A. Janssens and Dr C.H. Tyndale-Biscoe, Australian National University, and Dr. M. Griffiths and J.C. MacIlroy C.S.I.R.O., Division of Wildlife Research for supplying the tissue.     

A multi-component Fermi surface in the vortex state of an underdoped high-Tc superconductor

To understand the origin of superconductivity, it is crucial to ascertain the nature and origin of the primary carriers available to participate in pairing. Recent quantum oscillation experiments on high-transition-temperature (high-T(c)) copper oxide superconductors have revealed the existence of a Fermi surface akin to that in normal metals, comprising fermionic carriers that undergo orbital quantization. The unexpectedly small size of the observed carrier pocket, however, leaves open a variety of possibilities for the existence or form of any underlying magnetic order, and its relation to d-wave superconductivity. Here we report experiments on quantum oscillations in the magnetization (the de Haas-van Alphen effect) in superconducting YBa(2)Cu(3)O(6.51) that reveal more than one carrier pocket. In particular, we find evidence for the existence of a much larger pocket of heavier mass carriers playing a thermodynamically dominant role in this hole-doped superconductor. Importantly, characteristics of the multiple pockets within this more complete Fermi surface impose constraints on the wavevector of any underlying order and the location of the carriers in momentum space. These constraints enable us to construct a possible density-wave model with spiral or related modulated magnetic order, consistent with experimental observations.     

Reductive glutamine metabolism by IDH1 mediates lipogenesis under hypoxia

Acetyl coenzyme A (AcCoA) is the central biosynthetic precursor for fatty-acid synthesis and protein acetylation. In the conventional view of mammalian cell metabolism, AcCoA is primarily generated from glucose-derived pyruvate through the citrate shuttle and ATP citrate lyase in the cytosol. However, proliferating cells that exhibit aerobic glycolysis and those exposed to hypoxia convert glucose to lactate at near-stoichiometric levels, directing glucose carbon away from the tricarboxylic acid cycle and fatty-acid synthesis. Although glutamine is consumed at levels exceeding that required for nitrogen biosynthesis, the regulation and use of glutamine metabolism in hypoxic cells is not well understood. Here we show that human cells use reductive metabolism of α-ketoglutarate to synthesize AcCoA for lipid synthesis. This isocitrate dehydrogenase-1 (IDH1)-dependent pathway is active in most cell lines under normal culture conditions, but cells grown under hypoxia rely almost exclusively on the reductive carboxylation of glutamine-derived α-ketoglutarate for de novo lipogenesis. Furthermore, renal cell lines deficient in the von Hippel-Lindau tumour suppressor protein preferentially use reductive glutamine metabolism for lipid biosynthesis even at normal oxygen levels. These results identify a critical role for oxygen in regulating carbon use to produce AcCoA and support lipid synthesis in mammalian cells.     

Photosynthetic architecture differs in coastal and oceanic diatoms

Diatoms are a key taxon of eukaryotic phytoplankton and a major contributor to global carbon fixation. They are ubiquitous in the marine ecosystem despite marked gradients in environmental properties, such as dissolved iron concentrations, between coastal and oceanic waters. Previous studies have shown that offshore species of diatoms and other eukaryotic algae have evolved lower iron requirements to subsist in iron-poor oceanic waters, but the biochemical mechanisms responsible for their decreased iron demand are unknown. Here we show, using laboratory-cultured model species, a fundamental difference between a coastal and an oceanic diatom in their photosynthetic architecture. Specifically, the oceanic diatom had up to fivefold lower photosystem I and up to sevenfold lower cytochrome b6f complex concentrations than a coastal diatom. These changes to the photosynthetic apparatus markedly decrease the cellular iron requirements of the oceanic diatom but not its photosynthetic rates. However, oceanic diatoms might have also sacrificed their ability to acclimate to rapid fluctuations in light intensity--a characteristic of dynamic and turbid coastal waters. We suggest that diatoms, and probably other eukaryotic algal taxa, exploited this difference in the underwater light climate between oceanic and coastal waters, enabling them to decrease their iron requirements without compromising photosynthetic capacity. This adaptation probably facilitated the colonization of the open ocean by diatoms, and contributes to their persistence in this iron-impoverished environment.