Endonuclease G is a novel determinant of cardiac hypertrophy and mitochondrial function

Left ventricular mass (LVM) is a highly heritable trait and an independent risk factor for all-cause mortality. So far, genome-wide association studies have not identified the genetic factors that underlie LVM variation, and the regulatory mechanisms for blood-pressure-independent cardiac hypertrophy remain poorly understood. Unbiased systems genetics approaches in the rat now provide a powerful complementary tool to genome-wide association studies, and we applied integrative genomics to dissect a highly replicated, blood-pressure-independent LVM locus on rat chromosome 3p. Here we identified endonuclease G (Endog), which previously was implicated in apoptosis but not hypertrophy, as the gene at the locus, and we found a loss-of-function mutation in Endog that is associated with increased LVM and impaired cardiac function. Inhibition of Endog in cultured cardiomyocytes resulted in an increase in cell size and hypertrophic biomarkers in the absence of pro-hypertrophic stimulation. Genome-wide network analysis unexpectedly implicated ENDOG in fundamental mitochondrial processes that are unrelated to apoptosis. We showed direct regulation of ENDOG by ERR-α and PGC1α (which are master regulators of mitochondrial and cardiac function), interaction of ENDOG with the mitochondrial genome and ENDOG-mediated regulation of mitochondrial mass. At baseline, the Endog-deleted mouse heart had depleted mitochondria, mitochondrial dysfunction and elevated levels of reactive oxygen species, which were associated with enlarged and steatotic cardiomyocytes. Our study has further established the link between mitochondrial dysfunction, reactive oxygen species and heart disease and has uncovered a role for Endog in maladaptive cardiac hypertrophy.     

New record and southern range extension for the Mearn's grasshopper mouse ( Onychomys arenicola Mearns, 1896) in Veracruz, Mexico

Mearn’s grasshopper mouse ( Onychomys arenicola ) in Mexico is found primarily in the central and northern states. This is the first report of the genus Onychomys in the state of Veracruz, based on 7 captured specimens (3 collected). This finding extends the species’ known distribution by approximately 470 km east-southeast. In addition, this record increases the alpha diversity of terrestrial mammals for the state of Veracruz to 192 species.     

Defining the core Arabidopsis thaliana root microbiome

Land plants associate with a root microbiota distinct from the complex microbial community present in surrounding soil. The microbiota colonizing the rhizosphere (immediately surrounding the root) and the endophytic compartment (within the root) contribute to plant growth, productivity, carbon sequestration and phytoremediation. Colonization of the root occurs despite a sophisticated plant immune system, suggesting finely tuned discrimination of mutualists and commensals from pathogens. Genetic principles governing the derivation of host-specific endophyte communities from soil communities are poorly understood. Here we report the pyrosequencing of the bacterial 16S ribosomal RNA gene of more than 600 Arabidopsis thaliana plants to test the hypotheses that the root rhizosphere and endophytic compartment microbiota of plants grown under controlled conditions in natural soils are sufficiently dependent on the host to remain consistent across different soil types and developmental stages, and sufficiently dependent on host genotype to vary between inbred Arabidopsis accessions. We describe different bacterial communities in two geochemically distinct bulk soils and in rhizosphere and endophytic compartments prepared from roots grown in these soils. The communities in each compartment are strongly influenced by soil type. Endophytic compartments from both soils feature overlapping, low-complexity communities that are markedly enriched in Actinobacteria and specific families from other phyla, notably Proteobacteria. Some bacteria vary quantitatively between plants of different developmental stage and genotype. Our rigorous definition of an endophytic compartment microbiome should facilitate controlled dissection of plant-microbe interactions derived from complex soil communities.     

Molecular machines: nanomotor rotates microscale objects

Nanomachines of the future will require molecular-scale motors that can perform work and collectively induce controlled motion of much larger objects. We have designed a synthetic, light-driven molecular motor that is embedded in a liquid-crystal film and can rotate objects placed on the film that exceed the size of the motor molecule by a factor of 10,000. The changes in shape of the motor during the rotary steps cause a remarkable rotational reorganization of the liquid-crystal film and its surface relief, which ultimately causes the rotation of submillimetre-sized particles on the film.     

Global landscape of protein complexes in the yeast Saccharomyces cerevisiae

Identification of protein-protein interactions often provides insight into protein function, and many cellular processes are performed by stable protein complexes. We used tandem affinity purification to process 4,562 different tagged proteins of the yeast Saccharomyces cerevisiae. Each preparation was analysed by both matrix-assisted laser desorption/ionization-time of flight mass spectrometry and liquid chromatography tandem mass spectrometry to increase coverage and accuracy. Machine learning was used to integrate the mass spectrometry scores and assign probabilities to the protein-protein interactions. Among 4,087 different proteins identified with high confidence by mass spectrometry from 2,357 successful purifications, our core data set (median precision of 0.69) comprises 7,123 protein-protein interactions involving 2,708 proteins. A Markov clustering algorithm organized these interactions into 547 protein complexes averaging 4.9 subunits per complex, about half of them absent from the MIPS database, as well as 429 additional interactions between pairs of complexes. The data (all of which are available online) will help future studies on individual proteins as well as functional genomics and systems biology.     

Defective prelamin A processing and muscular and adipocyte alterations in Zmpste24 metalloproteinase-deficient mice

The mouse ortholog of human FACE-1, Zmpste24, is a multispanning membrane protein widely distributed in mammalian tissues and structurally related to Afc1p/ste24p, a yeast metalloproteinase involved in the maturation of fungal pheromones. Disruption of the gene Zmpste24 caused severe growth retardation and premature death in homozygous-null mice. Histopathological analysis of the mutant mice revealed several abnormalities, including dilated cardiomyopathy, muscular dystrophy and lipodystrophy. These alterations are similar to those developed by mice deficient in A-type lamin, a major component of the nuclear lamina, and phenocopy most defects observed in humans with diverse congenital laminopathies. In agreement with this finding, Zmpste24-null mice are defective in the proteolytic processing of prelamin A. This deficiency in prelamin A maturation leads to the generation of abnormalities in nuclear architecture that probably underlie the many phenotypes observed in both mice and humans with mutations in the lamin A gene. These results indicate that prelamin A is a specific substrate for Zmpste24 and demonstrate the usefulness of genetic approaches for identifying the in vivo substrates of proteolytic enzymes.     

Vapour undersaturation in primitive mid-ocean-ridge basalt and the volatile content of Earth's upper mantle

The analysis of volatiles in magmatic systems can be used to constrain the volatile content of the Earth's mantle and the influence that magmatic degassing has on the chemistry of the oceans and the atmosphere. But most volatile elements have very low solubilities in magmas at atmospheric pressure, and therefore virtually all erupted lavas are degassed and do not retain their primary volatile signatures. Here we report the undersaturated pre-eruptive volatile content for a suite of mid-ocean-ridge basalts from the Siqueiros intra-transform spreading centre. The undersaturation leads to correlations between volatiles and refractory trace elements that provide new constraints on volatile abundances and their behaviour in the upper mantle. Our data generate improved limits on the abundances of carbon dioxide, water, fluorine, sulphur and chlorine in the source of normal mid-ocean-ridge basalt. The incompatible behaviour of carbon dioxide, together with the CO(2)/Nb and CO(2)/Cl ratios, permit estimates of primitive carbon dioxide and chlorine to be made for degassed and chlorine-contaminated mid-ocean-ridge basalt magmas, and hence constrain degassing and contamination histories of mid-ocean ridges.     

Non-redundant role of the long pentraxin PTX3 in anti-fungal innate immune response

Pentraxins are a superfamily of conserved proteins that are characterized by a cyclic multimeric structure. The classical short pentraxins, C-reactive protein (CRP) and serum amyloid P component (SAP), are acute-phase proteins produced in the liver in response to inflammatory mediators. Short pentraxins regulate innate resistance to microbes and the scavenging of cellular debris and extracellular matrix components. In contrast, long pentraxins have an unrelated, long amino-terminal domain coupled to the carboxy-terminal pentraxin domain, and differ, with respect to short pentraxins, in their gene organization, chromosomal localization, cellular source, and in their stimuli-inducing and ligand-recognition ability. To investigate the in vivo function of the long pentraxin PTX3, we generated mice deficient in Ptx3 by homologous recombination. Ptx3-null mice were susceptible to invasive pulmonary aspergillosis. Ptx3 binds selected microbial agents, including conidia of Aspergillus fumigatus, and we found that susceptibility of Ptx3-null mice was associated with defective recognition of conidia by alveolar macrophages and dendritic cells, as well as inappropriate induction of an adaptive type 2 response. Thus, the long pentraxin Ptx3 is a secreted pattern-recognition receptor that has a non-redundant role in resistance to selected microbial agents, in particular to the opportunistic fungal pathogen Aspergillus fumigatus.     

Neuroanatomy: brain asymmetry and long-term memory

The asymmetrical positioning of neural structures on the left or right side of the brain in vertebrates and in invertebrates may be correlated with brain laterality, which is associated with cognitive skills. But until now this has not been illustrated experimentally. Here we describe an asymmetrically positioned brain structure in the fruitfly Drosophila and find that the small proportion of wild-type flies that have symmetrical brains with two such structures lack a normal long-term memory, although their short-term memory is intact. Our results indicate that brain asymmetry may be required for generating or retrieving long-term memory.