Nitric oxide regulates the heart by spatial confinement of nitric oxide synthase isoforms

Subcellular localization of nitric oxide (NO) synthases with effector molecules is an important regulatory mechanism for NO signalling. In the heart, NO inhibits L-type Ca2+ channels but stimulates sarcoplasmic reticulum (SR) Ca2+ release, leading to variable effects on myocardial contractility. Here we show that spatial confinement of specific NO synthase isoforms regulates this process. Endothelial NO synthase (NOS3) localizes to caveolae, where compartmentalization with beta-adrenergic receptors and L-type Ca2+ channels allows NO to inhibit beta-adrenergic-induced inotropy. Neuronal NO synthase (NOS1), however, is targeted to cardiac SR. NO stimulation of SR Ca2+ release via the ryanodine receptor (RyR) in vitro, suggests that NOS1 has an opposite, facilitative effect on contractility. We demonstrate that NOS1-deficient mice have suppressed inotropic response, whereas NOS3-deficient mice have enhanced contractility, owing to corresponding changes in SR Ca2+ release. Both NOS1-/- and NOS3-/- mice develop age-related hypertrophy, although only NOS3-/- mice are hypertensive. NOS1/3-/- double knockout mice have suppressed beta-adrenergic responses and an additive phenotype of marked ventricular remodelling. Thus, NOS1 and NOS3 mediate independent, and in some cases opposite, effects on cardiac structure and function.     

Geobacter metallireducens accesses insoluble Fe(III) oxide by chemotaxis

Microorganisms that use insoluble Fe(III) oxide as an electron acceptor can have an important function in the carbon and nutrient cycles of aquatic sediments and in the bioremediation of organic and metal contaminants in groundwater. Although Fe(III) oxides are often abundant, Fe(III)-reducing microbes are faced with the problem of how to access effectively an electron acceptor that can not diffuse to the cell. Fe(III)-reducing microorganisms in the genus Shewanella have resolved this problem by releasing soluble quinones that can carry electrons from the cell surface to Fe(III) oxide that is at a distance from the cell. Here we report that another Fe(III)-reducer, Geobacter metallireducens, has an alternative strategy for accessing Fe(III) oxides. Geobacter metallireducens specifically expresses flagella and pili only when grown on insoluble Fe(III) or Mn(IV) oxide, and is chemotactic towards Fe(II) and Mn(II) under these conditions. These results suggest that G. metallireducens senses when soluble electron acceptors are depleted and then synthesizes the appropriate appendages to permit it to search for, and establish contact with, insoluble Fe(III) or Mn(IV) oxide. This approach to the use of an insoluble electron acceptor may explain why Geobacter species predominate over other Fe(III) oxide-reducing microorganisms in a wide variety of sedimentary environments.     

Complete genome sequence of the model actinomycete Streptomyces coelicolor A3(2)

Streptomyces coelicolor is a representative of the group of soil-dwelling, filamentous bacteria responsible for producing most natural antibiotics used in human and veterinary medicine. Here we report the 8,667,507 base pair linear chromosome of this organism, containing the largest number of genes so far discovered in a bacterium. The 7,825 predicted genes include more than 20 clusters coding for known or predicted secondary metabolites. The genome contains an unprecedented proportion of regulatory genes, predominantly those likely to be involved in responses to external stimuli and stresses, and many duplicated gene sets that may represent 'tissue-specific' isoforms operating in different phases of colonial development, a unique situation for a bacterium. An ancient synteny was revealed between the central 'core' of the chromosome and the whole chromosome of pathogens Mycobacterium tuberculosis and Corynebacterium diphtheriae. The genome sequence will greatly increase our understanding of microbial life in the soil as well as aiding the generation of new drug candidates by genetic engineering.     

Ocean productivity before about 1.9 Gyr ago limited by phosphorus adsorption onto iron oxides

After the evolution of oxygen-producing cyanobacteria at some time before 2.7 billion years ago, oxygen production on Earth is thought to have depended on the availability of nutrients in the oceans, such as phosphorus (in the form of orthophosphate). In the modern oceans, a significant removal pathway for phosphorus occurs by way of its adsorption onto iron oxide deposits. Such deposits were thought to be more abundant in the past when, under low sulphate conditions, the formation of large amounts of iron oxides resulted in the deposition of banded iron formations. Under these circumstances, phosphorus removal by iron oxide adsorption could have been enhanced. Here we analyse the phosphorus and iron content of banded iron formations to show that ocean orthophosphate concentrations from 3.2 to 1.9 billion years ago (during the Archaean and early Proterozoic eras) were probably only approximately 10-25% of present-day concentrations. We suggest therefore that low phosphorus availability should have significantly reduced rates of photosynthesis and carbon burial, thereby reducing the long-term oxygen production on the early Earth--as previously speculated--and contributing to the low concentrations of atmospheric oxygen during the late Archaean and early Proterozoic.     

Low host specificity of herbivorous insects in a tropical forest

Two decades of research have not established whether tropical insect herbivores are dominated by specialists or generalists. This impedes our understanding of species coexistence in diverse rainforest communities. Host specificity and species richness of tropical insects are also key parameters in mapping global patterns of biodiversity. Here we analyse data for over 900 herbivorous species feeding on 51 plant species in New Guinea and show that most herbivorous species feed on several closely related plant species. Because species-rich genera are dominant in tropical floras, monophagous herbivores are probably rare in tropical forests. Furthermore, even between phylogenetically distant hosts, herbivore communities typically shared a third of their species. These results do not support the classical view that the coexistence of herbivorous species in the tropics is a consequence of finely divided plant resources; non-equilibrium models of tropical diversity should instead be considered. Low host specificity of tropical herbivores reduces global estimates of arthropod diversity from 31 million (ref. 1) to 4 6 million species. This finding agrees with estimates based on taxonomic collections, reconciling an order of magnitude discrepancy between extrapolations of global diversity based on ecological samples of tropical communities with those based on sampling regional faunas.     

Structural determinants for GoLoco-induced inhibition of nucleotide release by Galpha subunits

Heterotrimeric G-proteins bind to cell-surface receptors and are integral in transmission of signals from outside the cell. Upon activation of the Galpha subunit by binding of GTP, the Galpha and Gbetagamma subunits dissociate and interact with effector proteins for signal transduction. Regulatory proteins with the 19-amino-acid GoLoco motif can bind to Galpha subunits and maintain G-protein subunit dissociation in the absence of Galpha activation. Here we describe the structural determinants of GoLoco activity as revealed by the crystal structure of Galpha(i1) GDP bound to the GoLoco region of the 'regulator of G-protein signalling' protein RGS14. Key contacts are described between the GoLoco motif and Galpha protein, including the extension of GoLoco's highly conserved Asp/Glu-Gln-Arg triad into the nucleotide-binding pocket of Galpha to make direct contact with the GDP alpha- and beta-phosphates. The structural organization of the GoLoco Galpha(i1) complex, when combined with supporting data from domain-swapping experiments, suggests that the Galpha all-helical domain and GoLoco-region carboxy-terminal residues control the specificity of GoLoco Galpha interactions.     

Formation and propagation of matter-wave soliton trains

Attraction between the atoms of a Bose-Einstein condensate renders it unstable to collapse, although a condensate with a limited number of atoms can be stabilized by confinement in an atom trap. However, beyond this number the condensate collapses. Condensates constrained to one-dimensional motion with attractive interactions are predicted to form stable solitons, in which the attractive forces exactly compensate for wave-packet dispersion. Here we report the formation of bright solitons of (7)Li atoms in a quasi-one-dimensional optical trap, by magnetically tuning the interactions in a stable Bose-Einstein condensate from repulsive to attractive. The solitons are set in motion by offsetting the optical potential, and are observed to propagate in the potential for many oscillatory cycles without spreading. We observe a soliton train, containing many solitons; repulsive interactions between neighbouring solitons are inferred from their motion.     

A mouse Mecp2-null mutation causes neurological symptoms that mimic Rett syndrome

Rett syndrome (RTT) is an inherited neurodevelopmental disorder of females that occurs once in 10,000-15,000 births. Affected females develop normally for 6-18 months, but then lose voluntary movements, including speech and hand skills. Most RTT patients are heterozygous for mutations in the X-linked gene MECP2 (refs. 3-12), encoding a protein that binds to methylated sites in genomic DNA and facilitates gene silencing. Previous work with Mecp2-null embryonic stem cells indicated that MeCP2 is essential for mouse embryogenesis. Here we generate mice lacking Mecp2 using Cre-loxP technology. Both Mecp2-null mice and mice in which Mecp2 was deleted in brain showed severe neurological symptoms at approximately six weeks of age. Compensation for absence of MeCP2 in other tissues by MeCP1 (refs. 19,20) was not apparent in genetic or biochemical tests. After several months, heterozygous female mice also showed behavioral symptoms. The overlapping delay before symptom onset in humans and mice, despite their profoundly different rates of development, raises the possibility that stability of brain function, not brain development per se, is compromised by the absence of MeCP2.