BAI1 is an engulfment receptor for apoptotic cells upstream of the ELMO/Dock180/Rac module

Engulfment and subsequent degradation of apoptotic cells is an essential step that occurs throughout life in all multicellular organisms. ELMO/Dock180/Rac proteins are a conserved signalling module for promoting the internalization of apoptotic cell corpses; ELMO and Dock180 function together as a guanine nucleotide exchange factor (GEF) for the small GTPase Rac, and thereby regulate the phagocyte actin cytoskeleton during engulfment. However, the receptor(s) upstream of the ELMO/Dock180/Rac module are still unknown. Here we identify brain-specific angiogenesis inhibitor 1 (BAI1) as a receptor upstream of ELMO and as a receptor that can bind phosphatidylserine on apoptotic cells. BAI1 is a seven-transmembrane protein belonging to the adhesion-type G-protein-coupled receptor family, with an extended extracellular region and no known ligands. We show that BAI1 functions as an engulfment receptor in both the recognition and subsequent internalization of apoptotic cells. Through multiple lines of investigation, we identify phosphatidylserine, a key 'eat-me' signal exposed on apoptotic cells, as a ligand for BAI1. The thrombospondin type 1 repeats within the extracellular region of BAI1 mediate direct binding to phosphatidylserine. As with intracellular signalling, BAI1 forms a trimeric complex with ELMO and Dock180, and functional studies suggest that BAI1 cooperates with ELMO/Dock180/Rac to promote maximal engulfment of apoptotic cells. Last, decreased BAI1 expression or interference with BAI1 function inhibits the engulfment of apoptotic targets ex vivo and in vivo. Thus, BAI1 is a phosphatidylserine recognition receptor that can directly recruit a Rac-GEF complex to mediate the uptake of apoptotic cells.     

Structural basis for synthesis of inflammatory mediators by human leukotriene C4 synthase

Cysteinyl leukotrienes are key mediators in inflammation and have an important role in acute and chronic inflammatory diseases of the cardiovascular and respiratory systems, in particular bronchial asthma. In the biosynthesis of cysteinyl leukotrienes, conversion of arachidonic acid forms the unstable epoxide leukotriene A4 (LTA4). This intermediate is conjugated with glutathione (GSH) to produce leukotriene C4 (LTC4) in a reaction catalysed by LTC4 synthase: this reaction is the key step in cysteinyl leukotriene formation. Here we present the crystal structure of the human LTC4 synthase in its apo and GSH-complexed forms to 2.00 and 2.15 A resolution, respectively. The structure reveals a homotrimer, where each monomer is composed of four transmembrane segments. The structure of the enzyme in complex with substrate reveals that the active site enforces a horseshoe-shaped conformation on GSH, and effectively positions the thiol group for activation by a nearby arginine at the membrane-enzyme interface. In addition, the structure provides a model for how the omega-end of the lipophilic co-substrate is pinned at one end of a hydrophobic cleft, providing a molecular 'ruler' to align the reactive epoxide at the thiol of glutathione. This provides new structural insights into the mechanism of LTC4 formation, and also suggests that the observed binding and activation of GSH might be common for a family of homologous proteins important for inflammatory and detoxification responses.     

Lanthanide contraction and magnetism in the heavy rare earth elements

The heavy rare earth elements crystallize into hexagonally close packed (h.c.p.) structures and share a common outer electronic configuration, differing only in the number of 4f electrons they have. These chemically inert 4f electrons set up localized magnetic moments, which are coupled via an indirect exchange interaction involving the conduction electrons. This leads to the formation of a wide variety of magnetic structures, the periodicities of which are often incommensurate with the underlying crystal lattice. Such incommensurate ordering is associated with a 'webbed' topology of the momentum space surface separating the occupied and unoccupied electron states (the Fermi surface). The shape of this surface-and hence the magnetic structure-for the heavy rare earth elements is known to depend on the ratio of the interplanar spacing c and the interatomic, intraplanar spacing a of the h.c.p. lattice. A theoretical understanding of this problem is, however, far from complete. Here, using gadolinium as a prototype for all the heavy rare earth elements, we generate a unified magnetic phase diagram, which unequivocally links the magnetic structures of the heavy rare earths to their lattice parameters. In addition to verifying the importance of the c/a ratio, we find that the atomic unit cell volume plays a separate, distinct role in determining the magnetic properties: we show that the trend from ferromagnetism to incommensurate ordering as atomic number increases is connected to the concomitant decrease in unit cell volume. This volume decrease occurs because of the so-called lanthanide contraction, where the addition of electrons to the poorly shielding 4f orbitals leads to an increase in effective nuclear charge and, correspondingly, a decrease in ionic radii.     

Regional climate shifts caused by gradual global cooling in the Pliocene epoch

The Earth's climate has undergone a global transition over the past four million years, from warm conditions with global surface temperatures about 3 degrees C warmer than today, smaller ice sheets and higher sea levels to the current cooler conditions. Tectonic changes and their influence on ocean heat transport have been suggested as forcing factors for that transition, including the onset of significant Northern Hemisphere glaciation approximately 2.75 million years ago, but the ultimate causes for the climatic changes are still under debate. Here we compare climate records from high latitudes, subtropical regions and the tropics, indicating that the onset of large glacial/interglacial cycles did not coincide with a specific climate reorganization event at lower latitudes. The regional differences in the timing of cooling imply that global cooling was a gradual process, rather than the response to a single threshold or episodic event as previously suggested. We also find that high-latitude climate sensitivity to variations in solar heating increased gradually, culminating after cool tropical and subtropical upwelling conditions were established two million years ago. Our results suggest that mean low-latitude climate conditions can significantly influence global climate feedbacks.     

Proof and evolutionary analysis of ancient genome duplication in the yeast Saccharomyces cerevisiae

Whole-genome duplication followed by massive gene loss and specialization has long been postulated as a powerful mechanism of evolutionary innovation. Recently, it has become possible to test this notion by searching complete genome sequence for signs of ancient duplication. Here, we show that the yeast Saccharomyces cerevisiae arose from ancient whole-genome duplication, by sequencing and analysing Kluyveromyces waltii, a related yeast species that diverged before the duplication. The two genomes are related by a 1:2 mapping, with each region of K. waltii corresponding to two regions of S. cerevisiae, as expected for whole-genome duplication. This resolves the long-standing controversy on the ancestry of the yeast genome, and makes it possible to study the fate of duplicated genes directly. Strikingly, 95% of cases of accelerated evolution involve only one member of a gene pair, providing strong support for a specific model of evolution, and allowing us to distinguish ancestral and derived functions.     

The interface between silicon and a high-k oxide

The ability of the semiconductor industry to continue scaling microelectronic devices to ever smaller dimensions (a trend known as Moore's Law) is limited by quantum mechanical effects: as the thickness of conventional silicon dioxide (SiO(2)) gate insulators is reduced to just a few atomic layers, electrons can tunnel directly through the films. Continued device scaling will therefore probably require the replacement of the insulator with high-dielectric-constant (high-k) oxides, to increase its thickness, thus preventing tunnelling currents while retaining the electronic properties of an ultrathin SiO(2) film. Ultimately, such insulators will require an atomically defined interface with silicon without an interfacial SiO(2) layer for optimal performance. Following the first reports of epitaxial growth of AO and ABO(3) compounds on silicon, the formation of an atomically abrupt crystalline interface between strontium titanate and silicon was demonstrated. However, the atomic structure proposed for this interface is questionable because it requires silicon atoms that have coordinations rarely found elsewhere in nature. Here we describe first-principles calculations of the formation of the interface between silicon and strontium titanate and its atomic structure. Our study shows that atomic control of the interfacial structure by altering the chemical environment can dramatically improve the electronic properties of the interface to meet technological requirements. The interface structure and its chemistry may provide guidance for the selection process of other high-k gate oxides and for controlling their growth.     

Holocene lake deposits of Bosten Lake, southern Xinjiang, China

A 9.25-m-long sediment core from Bosten Lake,Xinjiang, provides detailed information about changes in the water budget and biological acticity over the last 8400 cal-endar years. The chronology is constructed from six AMS radiocarbon dates on the terrestrial plant remains. Based onanalyses of TOC, CO3, detrital compounds and biogenic SiO2,lake level fluctuations and periods of remarkably-negative water budget appeared at 8.4-8.2 cal ka, 7.38-7.25 cal ka,5.7-5.5 cal ka, 3.7-3.4 cal ka and 3.3-2.9 cal ka, respec-tively. As they are in-phase with low lake levels at Sumxl Co and Bangong Co in western Tibet Plateau and with paleo-lakes in Inner Mongolia, a climate-induced change to some-what drier and warmer conditions is inferred. A further drop in lake level after 1320 AD of about 200 yr duration may heattributed to a negative water balance prior to the main phase of the Little Ice Age. Deep and stable lake phases of 1500 yr and 1800 yr duration at 7.2-5.7 cal ka and 5.5-3.7cal ka coincide with maximum moisture during the Holocene Megathermai in China. The long term trend towards aridity since about 4.3 cal ka can dearly be recognised. The reduced water budget of Bosten Lake from 640-1200 AD may be attributed to local effects.     

Antiferromagnetic order as the competing ground state in electron-doped Nd1.85Ce0.15CuO4

Superconductivity in the high-transition-temperature (high-T(c)) copper oxides competes with other possible ground states. The physical explanation for superconductivity can be constrained by determining the nature of the closest competing ground state, and establishing if that state is universal among the high-T(c) materials. Antiferromagnetism has been theoretically predicted to be the competing ground state. A competing ground state is revealed when superconductivity is destroyed by the application of a magnetic field, and antiferromagnetism has been observed in hole-doped materials under the influence of modest fields. None of the previous experiments have revealed the quantum phase transition from the superconducting state to the antiferromagnetic state, because they failed to reach the upper critical field B(c2). Here we report the results of transport and neutron-scattering experiments on electron-doped Nd1.85Ce0.15CuO4 (refs 13, 14), where B(c2) can be reached. The applied field reveals a static, commensurate, anomalously conducting long-range ordered antiferromagnetic state, in which the induced moment scales approximately linearly with the field strength until it saturates at B(c2). This and previous experiments on the hole-doped materials therefore establishes antiferromagnetic order as a competing ground state in the high-T(c) copper oxide materials, irrespective of electron or hole doping.     

A preliminary study of crassulacean acid metabolism (CAM) in the endangered aquatic quillwortIsoetes sinensis Palmer in China

Isoetes sinensis Palmer (Isoetaceae) is an aquatic or amphibious plant that is critically endangered in China. Previous studies have revealed the crassulacean acid metabolism (CAM)-like photosynthetic pathway occurs commonly in submerged leaves in genusIsoetes. Water chemistry parameters and the titratable acidity content of the plant extract were measured from samples obtained in the early morning (7∶00) and late afternoon (15∶00) from twoI. sinensis populations in China. One population occurs in the eulittoral zone of a freshwater tidal river at low elevation (134 m) and another occurs in a densely vegetated, high elevation (1 100 m) alpine shallow pool. Significant differences in pH and titratable acidity of the plant extract were detected between the morning and afternoon samples. These changes are associated with diurnal changes in water chemistry. Our results provide the first evidence for the existence of the CAM pathway in the East Asian endemicIsoetes sinensis Palmer. The magnitude of fluctuations in the titratable acidity of the plant extract may be correlated with the severe carbon limitation imposed on the plants by its aquatic habitat. Foundation item: Supported by the State Key Basic Research and Development Plan (G2000046805) Biography:Pang Xin-an (1974-), male, Master candidate, research direction: conservation biology.