Angiotensin-converting enzyme 2 is an essential regulator of heart function

Cardiovascular diseases are predicted to be the most common cause of death worldwide by 2020. Here we show that angiotensin-converting enzyme 2 (ace2) maps to a defined quantitative trait locus (QTL) on the X chromosome in three different rat models of hypertension. In all hypertensive rat strains, ACE2 messenger RNA and protein expression were markedly reduced, suggesting that ace2 is a candidate gene for this QTL. Targeted disruption of ACE2 in mice results in a severe cardiac contractility defect, increased angiotensin II levels, and upregulation of hypoxia-induced genes in the heart. Genetic ablation of ACE on an ACE2 mutant background completely rescues the cardiac phenotype. But disruption of ACER, a Drosophila ACE2 homologue, results in a severe defect of heart morphogenesis. These genetic data for ACE2 show that it is an essential regulator of heart function in vivo.     

A synthetic multicellular system for programmed pattern formation

Pattern formation is a hallmark of coordinated cell behaviour in both single and multicellular organisms. It typically involves cell-cell communication and intracellular signal processing. Here we show a synthetic multicellular system in which genetically engineered 'receiver' cells are programmed to form ring-like patterns of differentiation based on chemical gradients of an acyl-homoserine lactone (AHL) signal that is synthesized by 'sender' cells. In receiver cells, 'band-detect' gene networks respond to user-defined ranges of AHL concentrations. By fusing different fluorescent proteins as outputs of network variants, an initially undifferentiated 'lawn' of receivers is engineered to form a bullseye pattern around a sender colony. Other patterns, such as ellipses and clovers, are achieved by placing senders in different configurations. Experimental and theoretical analyses reveal which kinetic parameters most significantly affect ring development over time. Construction and study of such synthetic multicellular systems can improve our quantitative understanding of naturally occurring developmental processes and may foster applications in tissue engineering, biomaterial fabrication and biosensing.     

Sulfatide-tenascin interaction mediates binding to the extracellular matrix and endocytic uptake of liposomes in glioma cells

Tenascin-C is an extracellular matrix glycoprotein, whose expression is highly restricted in normal adult tissues, but markedly up-regulated in a range of tumors, and therefore serves as a potential receptor for targeted anticancer drug or gene delivery. We describe here a liposomal carrier system in which the targeting ligand is sulfatide. Experiments with tenascin-C-expressing glioma cells demonstrated that binding of liposomes to the extracellular matrix relied essentially on the sulfatide-tenascin-C interaction. Following binding to the extracellular matrix, the sulfatide-containing liposomes were internalized via both caveolae/lipid raft- and clathrin-dependent pathways, which would ensure direct cytoplasmic release of the cargoes carried in the liposomes. Such natural lipid-guided intracellular delivery targeting at the extracellular matrix glycoproteins of tumor cells thus opens a new direction for development of more effective anticancer chemotherapeutics in future. K. Shao & Q. Hou: These authors contributed equally to this work. Received 22 September 2006; received after revision 5 December 2006; accepted 9 January 2007     

Formation of Kuiper-belt binaries by dynamical friction and three-body encounters

The Kuiper belt is a disk of icy bodies that orbit the Sun beyond Neptune; the largest known members are Pluto and its companion Charon. A few per cent of Kuiper-belt bodies have recently been found to be binaries with wide separations and mass ratios of the order of unity. Collisions were too infrequent to account for the observed number of binaries, implying that these binaries formed through collisionless interactions mediated by gravity. These interactions are likely to have been most effective during the period of runaway accretion, early in the Solar System's history. Here we show that a transient binary forms when two large bodies penetrate one another's Hill sphere (the region where their mutual forces are larger than the tidal force of the Sun). The loss of energy needed to stabilize the binary orbit can then occur either through dynamical friction from surrounding small bodies, or through the gravitational scattering of a third large body. Our estimates slightly favour the former mechanism. We predict that five per cent of Kuiper-belt objects are binaries with apparent separations greater than 0.2 arcsec, and that most are in tighter binaries or systems of higher multiplicity.     

Hot Jupiters from secular planet-planet interactions

About 25 per cent of 'hot Jupiters' (extrasolar Jovian-mass planets with close-in orbits) are actually orbiting counter to the spin direction of the star. Perturbations from a distant binary star companion can produce high inclinations, but cannot explain orbits that are retrograde with respect to the total angular momentum of the system. Such orbits in a stellar context can be produced through secular (that is, long term) perturbations in hierarchical triple-star systems. Here we report a similar analysis of planetary bodies, including both octupole-order effects and tidal friction, and find that we can produce hot Jupiters in orbits that are retrograde with respect to the total angular momentum. With distant stellar mass perturbers, such an outcome is not possible. With planetary perturbers, the inner orbit's angular momentum component parallel to the total angular momentum need not be constant. In fact, as we show here, it can even change sign, leading to a retrograde orbit. A brief excursion to very high eccentricity during the chaotic evolution of the inner orbit allows planet-star tidal interactions to rapidly circularize that orbit, decoupling the planets and forming a retrograde hot Jupiter.     

A satellite view of aerosols in the climate system

Anthropogenic aerosols are intricately linked to the climate system and to the hydrologic cycle. The net effect of aerosols is to cool the climate system by reflecting sunlight. Depending on their composition, aerosols can also absorb sunlight in the atmosphere, further cooling the surface but warming the atmosphere in the process. These effects of aerosols on the temperature profile, along with the role of aerosols as cloud condensation nuclei, impact the hydrologic cycle, through changes in cloud cover, cloud properties and precipitation. Unravelling these feedbacks is particularly difficult because aerosols take a multitude of shapes and forms, ranging from desert dust to urban pollution, and because aerosol concentrations vary strongly over time and space. To accurately study aerosol distribution and composition therefore requires continuous observations from satellites, networks of ground-based instruments and dedicated field experiments. Increases in aerosol concentration and changes in their composition, driven by industrialization and an expanding population, may adversely affect the Earth's climate and water supply.