A methylaspartate cycle in haloarchaea

Access to novel ecological niches often requires adaptation of metabolic pathways to cope with new environments. For conversion to cellular building blocks, many substrates enter central carbon metabolism via acetyl-coenzyme A (acetyl-CoA). Until now, only two such pathways have been identified: the glyoxylate cycle and the ethylmalonyl-CoA pathway. Prokaryotes in the haloarchaea use a third pathway by which acetyl-CoA is oxidized to glyoxylate via the key intermediate methylaspartate. Glyoxylate condensation with another acetyl-CoA molecule yields malate, the final assimilation product. This cycle combines reactions that originally belonged to different metabolic processes in different groups of prokaryotes, which suggests lateral gene transfer and evolutionary tinkering of acetate assimilation. Moreover, it requires elevated intracellular glutamate concentrations, as well as coupling carbon assimilation with nitrogen metabolism.     

Targeting of cyclic AMP degradation to beta 2-adrenergic receptors by beta-arrestins

Catecholamines signal through the beta2-adrenergic receptor by promoting production of the second messenger adenosine 3',5'-monophosphate (cAMP). The magnitude of this signal is restricted by desensitization of the receptors through their binding to beta-arrestins and by cAMP degradation by phosphodiesterase (PDE) enzymes. We show that beta-arrestins coordinate both processes by recruiting PDEs to activated beta2-adrenergic receptors in the plasma membrane of mammalian cells. In doing so, the beta-arrestins limit activation of membrane-associated cAMP-activated protein kinase by simultaneously slowing the rate of cAMP production through receptor desensitization and increasing the rate of its degradation at the membrane.     

Preindustrial to modern interdecadal variability in coral reef pH

The oceans are becoming more acidic due to absorption of anthropogenic carbon dioxide from the atmosphere. The impact of ocean acidification on marine ecosystems is unclear, but it will likely depend on species adaptability and the rate of change of seawater pH relative to its natural variability. To constrain the natural variability in reef-water pH, we measured boron isotopic compositions in a approximately 300-year-old massive Porites coral from the southwestern Pacific. Large variations in pH are found over approximately 50-year cycles that covary with the Interdecadal Pacific Oscillation of ocean-atmosphere anomalies, suggesting that natural pH cycles can modulate the impact of ocean acidification on coral reef ecosystems.     

Control of stress-dependent cardiac growth and gene expression by a microRNA

The heart responds to diverse forms of stress by hypertrophic growth accompanied by fibrosis and eventual diminution of contractility, which results from down-regulation of alpha-myosin heavy chain (alphaMHC) and up-regulation of betaMHC, the primary contractile proteins of the heart. We found that a cardiac-specific microRNA (miR-208) encoded by an intron of the alphaMHC gene is required for cardiomyocyte hypertrophy, fibrosis, and expression of betaMHC in response to stress and hypothyroidism. Thus, the alphaMHC gene, in addition to encoding a major cardiac contractile protein, regulates cardiac growth and gene expression in response to stress and hormonal signaling through miR-208.     

Regulation of cytokine receptors by Golgi N-glycan processing and endocytosis

The Golgi enzyme beta1,6 N-acetylglucosaminyltransferase V (Mgat5) is up-regulated in carcinomas and promotes the substitution of N-glycan with poly N-acetyllactosamine, the preferred ligand for galectin-3 (Gal-3). Here, we report that expression of Mgat5 sensitized mouse cells to multiple cytokines. Gal-3 cross-linked Mgat5-modified N-glycans on epidermal growth factor and transforming growth factor-beta receptors at the cell surface and delayed their removal by constitutive endocytosis. Mgat5 expression in mammary carcinoma was rate limiting for cytokine signaling and consequently for epithelial-mesenchymal transition, cell motility, and tumor metastasis. Mgat5 also promoted cytokine-mediated leukocyte signaling, phagocytosis, and extravasation in vivo. Thus, conditional regulation of N-glycan processing drives synchronous modification of cytokine receptors, which balances their surface retention against loss via endocytosis.     

A transient rise in tropical sea surface temperature during the Paleocene-Eocene thermal maximum

The Paleocene-Eocene Thermal Maximum (PETM) has been attributed to a rapid rise in greenhouse gas levels. If so, warming should have occurred at all latitudes, although amplified toward the poles. Existing records reveal an increase in high-latitude sea surface temperatures (SSTs) (8 degrees to 10 degrees C) and in bottom water temperatures (4 degrees to 5 degrees C). To date, however, the character of the tropical SST response during this event remains unconstrained. Here we address this deficiency by using paired oxygen isotope and minor element (magnesium/calcium) ratios of planktonic foraminifera from a tropical Pacific core to estimate changes in SST. Using mixed-layer foraminifera, we found that the combined proxies imply a 4 degrees to 5 degrees C rise in Pacific SST during the PETM. These results would necessitate a rise in atmospheric pCO2 to levels three to four times as high as those estimated for the late Paleocene.     

Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagy

Adenosine monophosphate-activated protein kinase (AMPK) is a conserved sensor of intracellular energy activated in response to low nutrient availability and environmental stress. In a screen for conserved substrates of AMPK, we identified ULK1 and ULK2, mammalian orthologs of the yeast protein kinase Atg1, which is required for autophagy. Genetic analysis of AMPK or ULK1 in mammalian liver and Caenorhabditis elegans revealed a requirement for these kinases in autophagy. In mammals, loss of AMPK or ULK1 resulted in aberrant accumulation of the autophagy adaptor p62 and defective mitophagy. Reconstitution of ULK1-deficient cells with a mutant ULK1 that cannot be phosphorylated by AMPK revealed that such phosphorylation is required for mitochondrial homeostasis and cell survival during starvation. These findings uncover a conserved biochemical mechanism coupling nutrient status with autophagy and cell survival.     

Synthesis and structure determination of the hierarchical meso-microporous zeolite ITQ-43

The formation of mesopores in microporous zeolites is generally performed by postsynthesis acid, basic, and steam treatments. The hierarchical pore systems thus formed allow better adsorption, diffusion, and reactivity of these materials. By combining organic and inorganic structure-directing agents and high-throughput methodologies, we were able to synthesize a zeolite with a hierarchical system of micropores and mesopores, with channel openings delimited by 28 tetrahedral atoms. Its complex crystalline structure was solved with the use of automated diffraction tomography.     

Varietal discrimination and genetic relationships of Vitis vinifera L. cultivars from two major Controlled Appellation (DOC) regions in Portugal

Thirty-nine grapevine cultivars widely grown in Portugal, especially in Vinhos Verdes and Douro regions, and two well known international cultivars as standards, were genotyped at 12 microsatellite loci. The number of alleles per locus ranged from 6 to 12, and the number of allelic combinations per locus from 13 to 26. The total number of unique genotypes in the 12 analysed loci was 120, having most of the cultivars (38 out of 41) at least one unique genotype in any of the loci. The microsatellite profiles were adequate to discriminate 41 cultivars. The level of observed heterozygosity at each locus varied from 70.7% to 95.1%. VVMD28 has been revealed as one of the most informative markers. Several synonymies between Spanish and Portuguese cultivars were confirmed, and some homonymies are discussed. The genetic profiles of all 41 cultivars were searched for possible parent-offspring groups. The data obtained revealed the possible descendence of Touriga Franca from Touriga Nacional and Marufo.