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.     

Mutant deoxynucleotide carrier is associated with congenital microcephaly

The disorder Amish microcephaly (MCPHA) is characterized by severe congenital microcephaly, elevated levels of alpha-ketoglutarate in the urine and premature death. The disorder is inherited in an autosomal recessive pattern and has been observed only in Old Order Amish families whose ancestors lived in Lancaster County, Pennsylvania. Here we show, by using a genealogy database and automated pedigree software, that 23 nuclear families affected with MCPHA are connected to a single ancestral couple. Through a whole-genome scan, fine mapping and haplotype analysis, we localized the gene affected in MCPHA to a region of 3 cM, or 2 Mb, on chromosome 17q25. We constructed a map of contiguous genomic clones spanning this region. One of the genes in this region, SLC25A19, which encodes a nuclear mitochondrial deoxynucleotide carrier (DNC), contains a substitution that segregates with the disease in affected individuals and alters an amino acid that is highly conserved in similar proteins. Functional analysis shows that the mutant DNC protein lacks the normal transport activity, implying that failed deoxynucleotide transport across the inner mitochondrial membrane causes MCPHA. Our data indicate that mitochondrial deoxynucleotide transport may be essential for prenatal brain growth.     

Mid-mantle deformation inferred from seismic anisotropy

With time, convective processes in the Earth's mantle will tend to align crystals, grains and inclusions. This mantle fabric is detectable seismologically, as it produces an anisotropy in material properties--in particular, a directional dependence in seismic-wave velocity. This alignment is enhanced at the boundaries of the mantle where there are rapid changes in the direction and magnitude of mantle flow, and therefore most observations of anisotropy are confined to the uppermost mantle or lithosphere and the lowermost-mantle analogue of the lithosphere, the D" region. Here we present evidence from shear-wave splitting measurements for mid-mantle anisotropy in the vicinity of the 660-km discontinuity, the boundary between the upper and lower mantle. Deep-focus earthquakes in the Tonga-Kermadec and New Hebrides subduction zones recorded at Australian seismograph stations record some of the largest values of shear-wave splitting hitherto reported. The results suggest that, at least locally, there may exist a mid-mantle boundary layer, which could indicate the impediment of flow between the upper and lower mantle in this region.     

Bose-Einstein condensation of atomic gases

The early experiments on Bose-Einstein condensation in dilute atomic gases accomplished three long-standing goals. First, cooling of neutral atoms into their motional ground state, thus subjecting them to ultimate control, limited only by Heisenberg's uncertainty relation. Second, creation of a coherent sample of atoms, in which all occupy the same quantum state, and the realization of atom lasers - devices that output coherent matter waves. And third, creation of a gaseous quantum fluid, with properties that are different from the quantum liquids helium-3 and helium-4. The field of Bose-Einstein condensation of atomic gases has continued to progress rapidly, driven by the combination of new experimental techniques and theoretical advances. The family of quantum-degenerate gases has grown, and now includes metastable and fermionic atoms. Condensates have become an ultralow-temperature laboratory for atom optics, collisional physics and many-body physics, encompassing phonons, superfluidity, quantized vortices, Josephson junctions and quantum phase transitions.     

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.     

Molecular identification of a danger signal that alerts the immune system to dying cells

In infections, microbial components provide signals that alert the immune system to danger and promote the generation of immunity. In the absence of such signals, there is often no immune response or tolerance may develop. This has led to the concept that the immune system responds only to antigens perceived to be associated with a dangerous situation such as infection. Danger signals are thought to act by stimulating dendritic cells to mature so that they can present foreign antigens and stimulate T lymphocytes. Dying mammalian cells have also been found to release danger signals of unknown identity. Here we show that uric acid is a principal endogenous danger signal released from injured cells. Uric acid stimulates dendritic cell maturation and, when co-injected with antigen in vivo, significantly enhances the generation of responses from CD8+ T cells. Eliminating uric acid in vivo inhibits the immune response to antigens associated with injured cells, but not to antigens presented by activated dendritic cells. Our findings provide a molecular link between cell injury and immunity and have important implications for vaccines, autoimmunity and inflammation.