Two pathways converge at CED-10 to mediate actin rearrangement and corpse removal in C. elegans

The removal of apoptotic cells is essential for the physiological well being of the organism. In Caenorhabditis elegans, two conserved, partially redundant genetic pathways regulate this process. In the first pathway, the proteins CED-2, CED-5 and CED-12 (mammalian homologues CrkII, Dock180 and ELMO, respectively) function to activate CED-10 (Rac1). In the second group, the candidate receptor CED-1 (CD91/LRP/SREC) probably recognizes an unknown ligand on the apoptotic cell and signals via its cytoplasmic tail to the adaptor protein CED-6 (hCED-6/GULP), whereas CED-7 (ABCA1) is thought to play a role in membrane dynamics. Molecular understanding of how the second pathway promotes engulfment of the apoptotic cell is lacking. Here, we show that CED-1, CED-6 and CED-7 are required for actin reorganization around the apoptotic cell corpse, and that CED-1 and CED-6 colocalize with each other and with actin around the dead cell. Furthermore, we find that the CED-10(Rac) GTPase acts genetically downstream of these proteins to mediate corpse removal, functionally linking the two engulfment pathways and identifying the CED-1, -6 and -7 signalling module as upstream regulators of Rac activation.     

Widespread magma oceans on asteroidal bodies in the early Solar System

Immediately following the formation of the Solar System, small planetary bodies accreted, some of which melted to produce igneous rocks. Over a longer timescale (15-33 Myr), the inner planets grew by incorporation of these smaller objects through collisions. Processes operating on such asteroids strongly influenced the final composition of these planets, including Earth. Currently there is little agreement about the nature of asteroidal igneous activity: proposals range from small-scale melting, to near total fusion and the formation of deep magma oceans. Here we report a study of oxygen isotopes in two basaltic meteorite suites, the HEDs (howardites, eucrites and diogenites, which are thought to sample the asteroid 4 Vesta) and the angrites (from an unidentified asteroidal source). Our results demonstrate that these meteorite suites formed during early, global-scale melting (> or = 50 per cent) events. We show that magma oceans were present on all the differentiated Solar System bodies so far sampled. Magma oceans produced compositionally layered planetesimals; the modification of such bodies before incorporation into larger objects can explain some anomalous planetary features, such as Earth's high Mg/Si ratio.     

Cortical growth marks reveal extended juvenile development in New Zealand moa

Cyclical growth marks in cortical bone, deposited before attainment of adult body size, reflect osteogenetic changes caused by annual rhythms and are a general phenomenon in non-avian ectothermic and endothermic tetrapods. However, the growth periods of ornithurines (the theropod group including all modern birds) are usually apomorphically shortened to less than a year, so annual growth marks are almost unknown in this group. Here we show that cortical growth marks are frequent in long bones of New Zealand's moa (Aves: Dinornithiformes), a recently extinct ratite order. Moa showed the exaggerated K-selected life-history strategy formerly common in the New Zealand avifauna, and in some instances took almost a decade to attain skeletal maturity. This indicates that reproductive maturity in moa was extremely delayed relative to all extant birds. The two presently recognized moa families (Dinornithidae and Emeidae) also showed different postnatal growth rates, which were associated with their relative differences in body size. Both species of giant Dinornis moa attained their massive stature (up to 240 kg live mass) by accelerating their juvenile growth rate compared to the smaller emeid moa species, rather than by extending the skeletal growth period.     

WNT7b mediates macrophage-induced programmed cell death in patterning of the vasculature

Macrophages have a critical role in inflammatory and immune responses through their ability to recognize and engulf apoptotic cells. Here we show that macrophages initiate a cell-death programme in target cells by activating the canonical WNT pathway. We show in mice that macrophage WNT7b is a short-range paracrine signal required for WNT-pathway responses and programmed cell death in the vascular endothelial cells of the temporary hyaloid vessels of the developing eye. These findings indicate that macrophages can use WNT ligands to influence cell-fate decisions--including cell death--in adjacent cells, and raise the possibility that they do so in many different cellular contexts.     

Unidirectional molecular motor on a gold surface

Molecules capable of mimicking the function of a wide range of mechanical devices have been fabricated, with motors that can induce mechanical movement attracting particular attention. Such molecular motors convert light or chemical energy into directional rotary or linear motion, and are usually prepared and operated in solution. But if they are to be used as nanomachines that can do useful work, it seems essential to construct systems that can function on a surface, like a recently reported linear artificial muscle. Surface-mounted rotors have been realized and limited directionality in their motion predicted. Here we demonstrate that a light-driven molecular motor capable of repetitive unidirectional rotation can be mounted on the surface of gold nanoparticles. The motor design uses a chiral helical alkene with an upper half that serves as a propeller and is connected through a carbon-carbon double bond (the rotation axis) to a lower half that serves as a stator. The stator carries two thiol-functionalized 'legs', which then bind the entire motor molecule to a gold surface. NMR spectroscopy reveals that two photo-induced cis-trans isomerizations of the central double bond, each followed by a thermal helix inversion to prevent reverse rotation, induce a full and unidirectional 360 degrees rotation of the propeller with respect to the surface-mounted lower half of the system.     

Glyoxalase 1 and glutathione reductase 1 regulate anxiety in mice

Anxiety and fear are normal emotional responses to threatening situations. In human anxiety disorders--such as panic disorder, obsessive-compulsive disorder, post-traumatic stress disorder, social phobia, specific phobias and generalized anxiety disorder--these responses are exaggerated. The molecular mechanisms involved in the regulation of normal and pathological anxiety are mostly unknown. However, the availability of different inbred strains of mice offers an excellent model system in which to study the genetics of certain behavioural phenotypes. Here we report, using a combination of behavioural analysis of six inbred mouse strains with quantitative gene expression profiling of several brain regions, the identification of 17 genes with expression patterns that correlate with anxiety-like behavioural phenotypes. To determine if two of the genes, glyoxalase 1 and glutathione reductase 1, have a causal role in the genesis of anxiety, we performed genetic manipulation using lentivirus-mediated gene transfer. Local overexpression of these genes in the mouse brain resulted in increased anxiety-like behaviour, while local inhibition of glyoxalase 1 expression by RNA interference decreased the anxiety-like behaviour. Both of these genes are involved in oxidative stress metabolism, linking this pathway with anxiety-related behaviour.     

Cycles in fossil diversity

It is well known that the diversity of life appears to fluctuate during the course of the Phanerozoic, the eon during which hard shells and skeletons left abundant fossils (0-542 million years ago). Here we show, using Sepkoski's compendium of the first and last stratigraphic appearances of 36,380 marine genera, a strong 62 +/- 3-million-year cycle, which is particularly evident in the shorter-lived genera. The five great extinctions enumerated by Raup and Sepkoski may be an aspect of this cycle. Because of the high statistical significance we also consider the contributions of environmental factors, and possible causes.