Science

Solution nuclear magnetic resonance structure of membrane-integral diacylglycerol kinase.

Publication Date: 2009 Jun 26 PMID: 19556511
Authors: Van Horn, W. D. - Kim, H. J. - Ellis, C. D. - Hadziselimovic, A. - Sulistijo, E. S. - Karra, M. D. - Tian, C. - Sonnichsen, F. D. - Sanders, C. R.
Journal: Science

Escherichia coli diacylglycerol kinase (DAGK) represents a family of integral membrane enzymes that is unrelated to all other phosphotransferases. We have determined the three-dimensional structure of the DAGK homotrimer with the use of solution nuclear magnetic resonance. The third transmembrane helix from each subunit is domain-swapped with the first and second transmembrane segments from an adjacent subunit. Each of DAGK's three active sites resembles a portico. The cornice of the portico appears to be the determinant of DAGK's lipid substrate specificity and overhangs the site of phosphoryl transfer near the water-membrane interface. Mutations to cysteine that caused severe misfolding were located in or near the active site, indicating a high degree of overlap between sites responsible for folding and for catalysis.

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Genomic footprints of a cryptic plastid endosymbiosis in diatoms.

Publication Date: 2009 Jun 26 PMID: 19556510
Authors: Moustafa, A. - Beszteri, B. - Maier, U. G. - Bowler, C. - Valentin, K. - Bhattacharya, D.
Journal: Science

Diatoms and other chromalveolates are among the dominant phytoplankters in the world's oceans. Endosymbiosis was essential to the success of chromalveolates, and it appears that the ancestral plastid in this group had a red algal origin via an ancient secondary endosymbiosis. However, recent analyses have turned up a handful of nuclear genes in chromalveolates that are of green algal derivation. Using a genome-wide approach to estimate the "green" contribution to diatoms, we identified >1700 green gene transfers, constituting 16% of the diatom nuclear coding potential. These genes were probably introduced into diatoms and other chromalveolates from a cryptic endosymbiont related to prasinophyte-like green algae. Chromalveolates appear to have recruited genes from the two major existing algal groups to forge a highly successful, species-rich protist lineage.

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Synthetic heterochromatin bypasses RNAi and centromeric repeats to establish functional centromeres.

Publication Date: 2009 Jun 26 PMID: 19556509
Authors: Kagansky, A. - Folco, H. D. - Almeida, R. - Pidoux, A. L. - Boukaba, A. - Simmer, F. - Urano, T. - Hamilton, G. L. - Allshire, R. C.
Journal: Science

In the central domain of fission yeast centromeres, the kinetochore is assembled on CENP-A(Cnp1) nucleosomes. Normally, small interfering RNAs generated from flanking outer repeat transcripts direct histone H3 lysine 9 methyltransferase Clr4 to homologous loci to form heterochromatin. Outer repeats, RNA interference (RNAi), and centromeric heterochromatin are required to establish CENP-A(Cnp1) chromatin. We demonstrated that tethering Clr4 via DNA-binding sites at euchromatic loci induces heterochromatin assembly, with or without active RNAi. This synthetic heterochromatin completely substitutes for outer repeats on plasmid-based minichromosomes, promoting de novo CENP-A(Cnp1) and kinetochore assembly, to allow their mitotic segregation, even with RNAi inactive. Thus, the role of outer repeats in centromere establishment is simply the provision of RNAi substrates to direct heterochromatin formation; H3K9 methylation-dependent heterochromatin is alone sufficient to form functional centromeres.

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Mitochondrial STAT3 supports Ras-dependent oncogenic transformation.

Publication Date: 2009 Jun 26 PMID: 19556508
Authors: Gough, D. J. - Corlett, A. - Schlessinger, K. - Wegrzyn, J. - Larner, A. C. - Levy, D. E.
Journal: Science

Signal transducer and activator of transcription 3 (STAT3) is a latent cytoplasmic transcription factor responsive to cytokine signaling and tyrosine kinase oncoproteins by nuclear translocation when it is tyrosine-phosphorylated. We report that malignant transformation by activated Ras is impaired without STAT3, in spite of the inability of Ras to drive STAT3 tyrosine phosphorylation or nuclear translocation. Moreover, STAT3 mutants that cannot be tyrosine-phosphorylated, that are retained in the cytoplasm, or that cannot bind DNA nonetheless supported Ras-mediated transformation. Unexpectedly, STAT3 was detected within mitochondria, and exclusive targeting of STAT3 to mitochondria without nuclear accumulation facilitated Ras transformation. Mitochondrial STAT3 sustained altered glycolytic and oxidative phosphorylation activities characteristic of cancer cells. Thus, in addition to its nuclear transcriptional role, STAT3 regulates a metabolic function in mitochondria, supporting Ras-dependent malignant transformation.

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Dynamic signaling network for the specification of embryonic pancreas and liver progenitors.

Publication Date: 2009 Jun 26 PMID: 19556507
Authors: Wandzioch, E. - Zaret, K. S.
Journal: Science

Studies of the formation of pancreas and liver progenitors have focused on individual inductive signals and cellular responses. Here, we investigated how bone morphogenetic protein, transforming growth factor-beta (TGFbeta), and fibroblast growth factor signaling pathways converge on the earliest genes that elicit pancreas and liver induction in mouse embryos. The inductive network was found to be dynamic; it changed within hours. Different signals functioned in parallel to induce different early genes, and two permutations of signals induced liver progenitor domains, which revealed flexibility in cell programming. Also, the specification of pancreas and liver progenitors was restricted by the TGFbeta pathway. These findings may enhance progenitor cell specification from stem cells for biomedical purposes and can help explain incomplete programming in stem cell differentiation protocols.

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Postmating sexual selection favors males that sire offspring with low fitness.

Publication Date: 2009 Jun 26 PMID: 19556506
Authors: Bilde, T. - Foged, A. - Schilling, N. - Arnqvist, G.
Journal: Science

Despite the costs of mating, females of most taxa mate with multiple males. Polyandrous females are hypothesized to gain genetic benefits for their offspring, but this assumes paternity bias favoring male genotypes that enhance offspring viability. We determined net male genetic effects on female and offspring fitness in a seed beetle and then tested whether fertilization success was biased in favor of high-quality male genotypes in double mating experiments. Contrary to expectations, high-quality male genotypes consistently had a lower postmating fertilization success in two independent assays. Our results imply that sexually antagonistic adaptations have a major and unappreciated influence on male postmating fertilization success. Such genetic variation renders indirect genetic benefits an unlikely driver of the evolution of polyandry.

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Trapping molecules on a chip.

Publication Date: 2009 Jun 26 PMID: 19556505
Authors: Meek, S. A. - Conrad, H. - Meijer, G.
Journal: Science

Magnetic trapping of atoms on chips has recently become straightforward, but analogous trapping of molecules has proved to be challenging. We demonstrated trapping of carbon monoxide molecules above a chip using direct loading from a supersonic beam. Upon arrival above the chip, the molecules are confined in tubular electric field traps approximately 20 micrometers in diameter, centered 25 micrometers above the chip, that move with the molecular beam at a velocity of several hundred meters per second. An array of these miniaturized moving traps is brought to a standstill over a distance of only a few centimeters. After a certain holding time, the molecules are accelerated off the chip again for detection. This loading and detection methodology is applicable to a wide variety of polar molecules, enabling the creation of a gas-phase molecular laboratory on a chip.

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White phosphorus is air-stable within a self-assembled tetrahedral capsule.

Publication Date: 2009 Jun 26 PMID: 19556504
Authors: Mal, P. - Breiner, B. - Rissanen, K. - Nitschke, J. R.
Journal: Science

The air-sensitive nature of white phosphorus underlies its destructive effect as a munition: Tetrahedral P4 molecules readily react with atmospheric dioxygen, leading this form of the element to spontaneously combust upon exposure to air. Here, we show that hydrophobic P4 molecules are rendered air-stable and water-soluble within the hydrophobic hollows of self-assembled tetrahedral container molecules, which form in water from simple organic subcomponents and iron(II) ions. This stabilization is not achieved through hermetic exclusion of O2 but rather by constriction of individual P4 molecules; the addition of oxygen atoms to P4 would result in the formation of oxidized species too large for their containers. The phosphorus can be released in controlled fashion without disrupting the cage by adding the competing guest benzene.

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High-resolution NMR in magnetic fields with unknown spatiotemporal variations.

Publication Date: 2009 Jun 26 PMID: 19556503
Authors: Pelupessy, P. - Rennella, E. - Bodenhausen, G.
Journal: Science

Nuclear magnetic resonance (NMR) experiments are usually carried out in homogeneous magnetic fields. In many cases, however, high-resolution spectra are virtually impossible to obtain because of the inherent heterogeneity of the samples or living organisms under investigation, as well as the poor homogeneity of the magnets (particularly when bulky samples must be placed outside their bores). Unstable power supplies and vibrations arising from cooling can lead to field fluctuations in time as well as space. We show how high-resolution NMR spectra can be obtained in inhomogeneous fields with unknown spatiotemporal variations. Our method, based on coherence transfer between spins, can accommodate spatial inhomogeneities of at least 11 gauss per centimeter and temporal fluctuations slower than 2 hertz.

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Elevated CO2 enhances otolith growth in young fish.

Publication Date: 2009 Jun 26 PMID: 19556502
Authors: Checkley, D. M. Jr - Dickson, A. G. - Takahashi, M. - Radich, J. A. - Eisenkolb, N. - Asch, R.
Journal: Science

A large fraction of the carbon dioxide added to the atmosphere by human activity enters the sea, causing ocean acidification. We show that otoliths (aragonite ear bones) of young fish grown under high CO2 (low pH) conditions are larger than normal, contrary to expectation. We hypothesize that CO2 moves freely through the epithelium around the otoliths in young fish, accelerating otolith growth while the local pH is controlled. This is the converse of the effect commonly reported for structural biominerals.

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Competitive interactions between cells: death, growth, and geography.

Publication Date: 2009 Jun 26 PMID: 19556501
Authors: Johnston, L. A.
Journal: Science

Competitive interactions between cells are the basis of many homeostatic processes in biology. Some of the best-described cases of competition between cells occur in Drosophila: cell competition, whereby somatic cells within a growing epithelium compete with one another for contribution to the adult, and stem cell competition, in which germline or somatic stem cells vie for residency in the niche. Both types of competition are conserved physiological processes, with much to tell us about how cellular neighborhoods influence cell behavior, and have importance to stem cell biology, regeneration and transplantation, and cancer.

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Growth factors, matrices, and forces combine and control stem cells.

Publication Date: 2009 Jun 26 PMID: 19556500
Authors: Discher, D. E. - Mooney, D. J. - Zandstra, P. W.
Journal: Science

Stem cell fate is influenced by a number of factors and interactions that require robust control for safe and effective regeneration of functional tissue. Coordinated interactions with soluble factors, other cells, and extracellular matrices define a local biochemical and mechanical niche with complex and dynamic regulation that stem cells sense. Decellularized tissue matrices and synthetic polymer niches are being used in the clinic, and they are also beginning to clarify fundamental aspects of how stem cells contribute to homeostasis and repair, for example, at sites of fibrosis. Multifaceted technologies are increasingly required to produce and interrogate cells ex vivo, to build predictive models, and, ultimately, to enhance stem cell integration in vivo for therapeutic benefit.

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The increasing complexity of the cancer stem cell paradigm.

Publication Date: 2009 Jun 26 PMID: 19556499
Authors: Rosen, J. M. - Jordan, C. T.
Journal: Science

The investigation and study of cancer stem cells (CSCs) have received enormous attention over the past 5 to 10 years but remain topics of considerable controversy. Opinions about the validity of the CSC hypothesis, the biological properties of CSCs, and the relevance of CSCs to cancer therapy differ widely. In the following commentary, we discuss the nature of the debate, the parameters by which CSCs can or cannot be defined, and the identification of new potential therapeutic targets elucidated by considering cancer as a problem in stem cell biology.

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The role of stromal stem cells in tissue regeneration and wound repair.

Publication Date: 2009 Jun 26 PMID: 19556498
Authors: Stappenbeck, T. S. - Miyoshi, H.
Journal: Science

The process of wound repair in epithelium-lined organs of mammals is complex and is influenced by numerous secreted factors including cytokines, growth factors, and chemokines. However, the cellular organizers of this process are still not understood. Recent studies of tissue regeneration in organisms with simpler development have uncovered details about the activity of stem cells in the mesenchyme (the blastema) during this process. These blastemal cells are well positioned to interpret cues from the environment and to execute decisions about the direction of wound repair. In mammalian wounds, stromal stem cells appear to be positioned to perform functions similar to those of blastemal cells, including communication with both the overlying epithelium and the inflammatory cells in the mesenchyme.

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Medical innovation versus stem cell tourism.

Publication Date: 2009 Jun 26 PMID: 19556497
Authors: Lindvall, O. - Hyun, I.
Journal: Science

Stem cell tourism is criticized on grounds of consumer fraud, blatant lack of scientific justification, and patient safety. However, the issues are complex because they invoke questions concerning the limits of acceptable medical innovation and medical travel. Here we discuss these issues and articulate conditions under which "unproven" therapies may be offered to patients outside of regular clinical trials.

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FDA regulation of stem cell-based products.

Publication Date: 2009 Jun 26 PMID: 19556496
Authors: Fink, D. W. Jr
Journal: Science

Cell self-renewal and the capacity to differentiate into multiple cell types (pluripotency) are biological attributes casting stem cells as attractive candidates for development of therapies targeting indications that involve functional restoration of damaged tissues. In the United States, clinical trials designed to demonstrate the safety and effectiveness of stem cell-based products are regulated by the U.S. Food and Drug Administration (FDA). To ensure that subjects enrolled in a clinical study involving stem cell-based products are not exposed to significant and unreasonable risk, the FDA reviews medical and scientific information that encompasses delineation of product-specific characteristics and preclinical testing to determine whether there is sufficient safety assurance to permit initiation of human clinical studies.

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Steps to the clinic. Stem cells. Introduction.

Publication Date: 2009 Jun 26 PMID: 19556495
Authors: Purnell, B. A. - Hines, P. J.
Journal: Science

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Computer science. Building an open Cloud.

Publication Date: 2009 Jun 26 PMID: 19556494
Authors: Nelson, M. R.
Journal: Science

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Chemistry. Rate control and reaction engineering.

Publication Date: 2009 Jun 26 PMID: 19556493
Authors: Norskov, J. K. - Bligaard, T. - Kleis, J.
Journal: Science

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Developmental biology. Phase transition in a cell.

Publication Date: 2009 Jun 26 PMID: 19556492
Authors: Le Goff, L. - Lecuit, T.
Journal: Science

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Evolution. Auxin at the evo-devo intersection.

Publication Date: 2009 Jun 26 PMID: 19556491
Authors: Friedman, W. E.
Journal: Science

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Microbiology. Seeing green and red in diatom genomes.

Publication Date: 2009 Jun 26 PMID: 19556490
Authors: Dagan, T. - Martin, W.
Journal: Science

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Information technology. Innovating education in Croatia.

Publication Date: 2009 Jun 26 PMID: 19556489
Authors: Primorac, D.
Journal: Science

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Research ethics. The NIH draft guidelines on human stem cell research.

Publication Date: 2009 Jun 26 PMID: 19556488
Authors: Majumder, M. A. - Cohen, C. B.
Journal: Science

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Creationist beliefs in Europe.

Publication Date: 2009 Jun 26 PMID: 19556487
Authors: Clement, P. - Quessada, M. P.
Journal: Science

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Sex in leishmania.

Publication Date: 2009 Jun 26 PMID: 19556486
Authors: Volf, P. - Sadlova, J.
Journal: Science

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Current Brazilian law on animal experimentation.

Publication Date: 2009 Jun 26 PMID: 19556485
Authors: Saldanha Machado, C. J. - Tereza, A. - Filipecki, P. - Teixeira, M.
Journal: Science

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The global alliance for chronic diseases.

Publication Date: 2009 Jun 26 PMID: 19556484
Authors: Daar, A. S. - Nabel, E. G. - Pramming, S. K. - Anderson, W. - Beaudet, A. - Liu, D. - Katoch, V. M. - Borysiewicz, L. K. - Glass, R. I. - Bell, J.
Journal: Science

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Space weather forecasting. Are we ready for the next solar maximum? No way, say scientists.

Publication Date: 2009 Jun 26 PMID: 19556483
Authors: Kerr, R. A.
Journal: Science

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Microbiology. Antibiotics in nature: beyond biological warfare.

Publication Date: 2009 Jun 26 PMID: 19556482
Authors: Mlot, C.
Journal: Science

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The brain collector.

Publication Date: 2009 Jun 26 PMID: 19556481
Authors: Miller, G.
Journal: Science

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Biodiversity. Biodiversity databases spread, prompting unification call.

Publication Date: 2009 Jun 26 PMID: 19556479
Authors: Thomas, C.
Journal: Science

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Science in society. China reins in wilder impulses in treatment of 'Internet addiction'.

Publication Date: 2009 Jun 26 PMID: 19556477
Authors: Stone, R.
Journal: Science

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International collaboration. Bioscientists slowly bridge the Taiwan Strait.

Publication Date: 2009 Jun 26 PMID: 19556476
Authors: Normile, D.
Journal: Science

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Depression gene. Back to the drawing board for psychiatric genetics.

Publication Date: 2009 Jun 26 PMID: 19556475
Authors: Holden, C.
Journal: Science

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Fusion research. ITER gets the nod for slower, step-by-step approach.

Publication Date: 2009 Jun 26 PMID: 19556474
Authors: Clery, D.
Journal: Science

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Biosecurity. Discovery of untracked pathogen vials at army lab sparks concerns.

Publication Date: 2009 Jun 26 PMID: 19556473
Authors: Bhattacharjee, Y.
Journal: Science

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Out with the old, in with the new?

Publication Date: 2009 Jun 26 PMID: 19556472
Authors: Pedersen, R.
Journal: Science

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Measuring the Cosmic Ray Acceleration Efficiency of a Supernova Remnant.

Publication Date: 2009 Jun 25 PMID: 19556465
Authors: Helder, E. A. - Vink, J. - Bassa, C. G. - Bamba, A. - Bleeker, J. A. - Funk, S. - Ghavamian, P. - van der Heyden, K. J. - Verbunt, F. - Yamazaki, R.
Journal: Science

Cosmic rays are the most energetic particles arriving at Earth. Although most of them are thought to be accelerated by supernova remnants, the details of the acceleration process and its efficiency are not well determined. Here, we show that the pressure induced by cosmic rays exceeds the thermal pressure behind the northeast shock of the supernova remnant RCW 86, where the x-ray emission is dominated by synchrotron radiation from ultra-relativistic electrons. We determined the cosmic-ray content from the thermal Doppler broadening measured with optical spectroscopy, combined with a proper-motion study in x-rays. The measured post-shock proton temperature in combination with the shock velocity does not agree with standard shock heating, implying that >50% of the post-shock pressure is produced by cosmic rays.

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DICER1 Mutations in Familial Pleuropulmonary Blastoma.

Publication Date: 2009 Jun 25 PMID: 19556464
Authors: Hill, D. A. - Ivanovich, J. - Priest, J. R. - Gurnett, C. A. - Dehner, L. P. - Desruisseau, D. - Jarzembowski, J. A. - Wikenheiser-Brokamp, K. A. - Suarez, B. K. - Whelan, A. J. - Williams, G. - Bracamontes, D. - Messinger, Y. - Goodfellow, P. J.
Journal: Science

Pleuropulmonary blastoma (PPB) is a rare pediatric lung tumor that is often part of an inherited cancer syndrome. PPBs consist of mesenchymal cells that are susceptible to malignant transformation and cysts lined by epithelial cells. In a subset of patients, overgrowth of the cysts by mesenchymal cells leads to sarcoma formation. Here, we show that 11 multiplex PPB families harbor heterozygous germline mutations in DICER1, a gene encoding an endoribonuclease critical to the generation of small noncoding regulatory RNAs. Expression of DICER1 protein was undetectable in the epithelial component of PPB tumors but was retained in the malignant mesenchyme (sarcoma). We hypothesize that loss of DICER1 in the epithelium of the developing lung alters the regulation of diffusible factors that promote mesenchymal proliferation.

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A Gene Network Regulating Lysosomal Biogenesis and Function.

Publication Date: 2009 Jun 25 PMID: 19556463
Authors: Sardiello, M. - Palmieri, M. - di Ronza, A. - Medina, D. L. - Valenza, M. - Gennarino, V. A. - Di Malta, C. - Donaudy, F. - Embrione, V. - Polishchuk, R. S. - Banfi, S. - Parenti, G. - Cattaneo, E. - Ballabio, A.
Journal: Science

Lysosomes are organelles central to degradation and recycling processes in animal cells. Whether lysosomal activity is coordinated to respond to cellular needs remains unclear. We found that most lysosomal genes exhibit coordinated transcriptional behavior and are regulated by the transcription factor TFEB. Under aberrant lysosomal storage conditions, TFEB translocated from the cytoplasm to the nucleus, resulting in the activation of its target genes. TFEB overexpression in cultured cells induced lysosomal biogenesis and increased the degradation of complex molecules, such as glycosaminoglycans (GAGs) and the pathogenic protein causing Huntington disease. Thus, a genetic program controls lysosomal biogenesis and function, providing a potential therapeutic target to enhance cellular clearing in lysosomal storage disorders and neurodegenerative diseases.

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String Theory, Quantum Phase Transitions, and the Emergent Fermi Liquid.

Publication Date: 2009 Jul 2 PMID: 19556462
Authors: Cubrovic, M. - Zaanen, J. - Schalm, K.
Journal: Science

A central problem in quantum condensed matter physics is the critical theory governing the zero-temperature quantum phase transition between strongly renormalized Fermi-liquids as found in heavy fermion intermetallics and possibly high Tc superconductors. Here, we present results showing that the mathematics of string theory is capable of describing such fermionic quantum critical states. Using the Anti-de-Sitter/Conformal Field Theory (AdS/CFT) correspondence to relate fermionic quantum critical fields to a gravitational problem, we compute the spectral functions of fermions in the field theory. By increasing the fermion density away from the relativistic quantum critical point, a state emerges with all the features of the Fermi-liquid.

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An ER-Mitochondria Tethering Complex Revealed by a Synthetic Biology Screen.

Publication Date: 2009 Jun 25 PMID: 19556461
Authors: Kornmann, B. - Currie, E. - Collins, S. R. - Schuldiner, M. - Nunnari, J. - Weissman, J. S. - Walter, P.
Journal: Science

Communication between organelles is an important feature of all eukaryotic cells. To uncover components involved in mitochondria/endoplasmic reticulum (ER) junctions, we screened for mutants that could be complemented by a synthetic protein designed to artificially tether the two organelles. We identified the Mmm1/Mdm10/Mdm12/Mdm34 complex as a molecular tether between ER and mitochondria. The tethering complex was composed of proteins resident of both ER and mitochondria. Using genome-wide mapping of genetic interactions, we showed that the components of the tethering complex were functionally connected to phospholipid biosynthesis and calcium signaling genes. In mutant cells, phospholipid biosynthesis was impaired. The tethering complex localized to discrete foci, suggesting that discrete sites of close apposition between ER and mitochondria facilitate interorganelle calcium and phospholipid exchange.

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Merkel cells are essential for light-touch responses.

Publication Date: 2009 Jun 19 PMID: 19541997
Authors: Maricich, S. M. - Wellnitz, S. A. - Nelson, A. M. - Lesniak, D. R. - Gerling, G. J. - Lumpkin, E. A. - Zoghbi, H. Y.
Journal: Science

The peripheral nervous system detects different somatosensory stimuli, including pain, temperature, and touch. Merkel cell-neurite complexes are touch receptors composed of sensory afferents and Merkel cells. The role that Merkel cells play in light-touch responses has been the center of controversy for over 100 years. We used Cre-loxP technology to conditionally delete the transcription factor Atoh1 from the body skin and foot pads of mice. Merkel cells are absent from these areas in Atoh1(CKO) animals. Ex vivo skin/nerve preparations from Atoh1(CKO) animals demonstrate complete loss of the characteristic neurophysiologic responses normally mediated by Merkel cell-neurite complexes. Merkel cells are, therefore, required for the proper encoding of Merkel receptor responses, suggesting that these cells form an indispensible part of the somatosensory system.

MeSH Categories: Animals, Basic Helix-Loop-Helix Transcription Factors/genetics/metabolism, Female, Foot, Male, Merkel Cells/metabolism/*physiology, Mice, Mice, Inbred C57BL, Mice, Knockout, Skin/cytology, *Skin Physiological Phenomena, Touch/*physiology

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Rapid and accurate large-scale coestimation of sequence alignments and phylogenetic trees.

Publication Date: 2009 Jun 19 PMID: 19541996
Authors: Liu, K. - Raghavan, S. - Nelesen, S. - Linder, C. R. - Warnow, T.
Journal: Science

Inferring an accurate evolutionary tree of life requires high-quality alignments of molecular sequence data sets from large numbers of species. However, this task is often difficult, slow, and idiosyncratic, especially when the sequences are highly diverged or include high rates of insertions and deletions (collectively known as indels). We present SATe (simultaneous alignment and tree estimation), an automated method to quickly and accurately estimate both DNA alignments and trees with the maximum likelihood criterion. In our study, it improved tree and alignment accuracy compared to the best two-phase methods currently available for data sets of up to 1000 sequences, showing that coestimation can be both rapid and accurate in phylogenetic studies.

MeSH Categories: Algorithms, Automation, Computer Simulation, DNA, Evolution, Molecular, Likelihood Functions, *Phylogeny, *Sequence Alignment/methods, *Software

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Fossil plant relative abundances indicate sudden loss of Late Triassic biodiversity in East Greenland.

Publication Date: 2009 Jun 19 PMID: 19541995
Authors: McElwain, J. C. - Wagner, P. J. - Hesselbo, S. P.
Journal: Science

The pace of Late Triassic (LT) biodiversity loss is uncertain, yet it could help to decipher causal mechanisms of mass extinction. We investigated relative abundance distributions (RADs) of six LT plant assemblages from the Kap Stewart Group, East Greenland, to determine the pace of collapse of LT primary productivity. RADs displayed not simply decreases in the number of taxa, but decreases in the number of common taxa. Likelihood tests rejected a hypothesis of continuously declining diversity. Instead, the RAD shift occurred over the upper two-to-four fossil plant assemblages and most likely over the last three (final 13 meters), coinciding with increased atmospheric carbon dioxide concentration and global warming. Thus, although the LT event did not induce mass extinction of plant families, it accompanied major and abrupt change in their ecology and diversity.

MeSH Categories: *Biodiversity, Evolution, *Extinction, Biological, *Fossils, Greenland, Likelihood Functions, Models, Biological, *Plants/genetics

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Atmospheric carbon dioxide concentration across the mid-Pleistocene transition.

Publication Date: 2009 Jun 19 PMID: 19541994
Authors: Honisch, B. - Hemming, N. G. - Archer, D. - Siddall, M. - McManus, J. F.
Journal: Science

The dominant period of Pleistocene glacial cycles changed during the mid-Pleistocene from 40,000 years to 100,000 years, for as yet unknown reasons. Here we present a 2.1-million-year record of sea surface partial pressure of CO2 (Pco2), based on boron isotopes in planktic foraminifer shells, which suggests that the atmospheric partial pressure of CO2 (pco2) was relatively stable before the mid-Pleistocene climate transition. Glacial Pco2 was approximately 31 microatmospheres higher before the transition (more than 1 million years ago), but interglacial Pco2 was similar to that of late Pleistocene interglacial cycles (<450,000 years ago). These estimates are consistent with a close linkage between atmospheric CO2 concentration and global climate, but the lack of a gradual decrease in interglacial Pco2 does not support the suggestion that a long-term drawdown of atmospheric CO2 was the main cause of the climate transition.

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Aggregation-induced dissociation of HCl(H2O)4 below 1 K: the smallest droplet of acid.

Publication Date: 2009 Jun 19 PMID: 19541993
Authors: Gutberlet, A. - Schwaab, G. - Birer, O. - Masia, M. - Kaczmarek, A. - Forbert, H. - Havenith, M. - Marx, D.
Journal: Science

Acid dissociation and the subsequent solvation of the charged fragments at ultracold temperatures in nanoenvironments, as distinct from ambient bulk water, are relevant to atmospheric and interstellar chemistry but remain poorly understood. Here we report the experimental observation of a nanoscopic aqueous droplet of acid formed within a superfluid helium cluster at 0.37 kelvin. High-resolution mass-selective infrared laser spectroscopy reveals that successive aggregation of the acid HCl with water molecules, HCl(H2O)n, readily results in the formation of hydronium at n = 4. Accompanying ab initio simulations show that undissociated clusters assemble by stepwise water molecule addition in electrostatic steering arrangements up to n = 3. Adding a fourth water molecule to the ringlike undissociated HCl(H2O)3 then spontaneously yields the compact dissociated H3O+(H2O)3Cl- ion pair. This aggregation mechanism bypasses deep local energy minima on the n = 4 potential energy surface and offers a general paradigm for reactivity at ultracold temperatures.

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Colloidal quantum-dot photodetectors exploiting multiexciton generation.

Publication Date: 2009 Jun 19 PMID: 19541992
Authors: Sukhovatkin, V. - Hinds, S. - Brzozowski, L. - Sargent, E. H.
Journal: Science

Multiexciton generation (MEG) has been indirectly observed in colloidal quantum dots, both in solution and the solid state, but has not yet been shown to enhance photocurrent in an optoelectronic device. Here, we report a class of solution-processed photoconductive detectors, sensitive in the ultraviolet, visible, and the infrared, in which the internal gain is dramatically enhanced for photon energies Ephoton greater than 2.7 times the quantum-confined bandgap Ebandgap. Three thin-film devices with different quantum-confined bandgaps (set by the size of their constituent lead sulfide nanoparticles) show enhancement determined by the bandgap-normalized photon energy, Ephoton/Ebandgap, which is a clear signature of MEG. The findings point to a valuable role for MEG in enhancing the photocurrent in a solid-state optoelectronic device. We compare the conditions on carrier excitation, recombination, and transport for photoconductive versus photovoltaic devices to benefit from MEG.

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Solar-like oscillations in a massive star.

Publication Date: 2009 Jun 19 PMID: 19541991
Authors: Belkacem, K. - Samadi, R. - Goupil, M. J. - Lefevre, L. - Baudin, F. - Deheuvels, S. - Dupret, M. A. - Appourchaux, T. - Scuflaire, R. - Auvergne, M. - Catala, C. - Michel, E. - Miglio, A. - Montalban, J. - Thoul, A. - Talon, S. - Baglin, A. - Noels, A.
Journal: Science

Seismology of stars provides insight into the physical mechanisms taking place in their interior, with modes of oscillation probing different layers. Low-amplitude acoustic oscillations excited by turbulent convection were detected four decades ago in the Sun and more recently in low-mass main-sequence stars. Using data gathered by the Convection Rotation and Planetary Transits mission, we report here on the detection of solar-like oscillations in a massive star, V1449 Aql, which is a known large-amplitude (beta Cephei) pulsator.

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Sexual intercourse involving giant sperm in Cretaceous ostracode.

Publication Date: 2009 Jun 19 PMID: 19541990
Authors: Matzke-Karasz, R. - Smith, R. J. - Symonova, R. - Miller, C. G. - Tafforeau, P.
Journal: Science

Reproduction with giant sperm occurs in distinct groups scattered over the animal kingdom. Although experiments in Drosophila assessed the influence of different selection pressures on this character, no information was available on its long-term stability. Sub-micrometer-resolution synchrotron quantitative phase tomography (holotomography) of exceptionally well-preserved three-dimensional Cretaceous ostracode fossils from the Brazilian Santana Formation indicates that ostracode reproduction with giant sperm persisted for at least over the past 100 million years. Remnants of the male sperm pumps as well as giant, inflated female sperm receptacles evidence that, despite high costs, reproduction with giant sperm can be an evolutionary successful strategy.

MeSH Categories: Animals, Brazil, Cell Size, Copulation/*physiology, Crustacea/anatomy & histology/cytology/*physiology, Evolution, Female, Fossils, Genitalia, Female/anatomy & histology, Genitalia, Male/anatomy & histology, Humans, Male, Spermatozoa/cytology/*physiology, Tomography, X-Ray Computed/methods

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Graphene: status and prospects.

Publication Date: 2009 Jun 19 PMID: 19541989
Authors: Geim, A. K.
Journal: Science

Graphene is a wonder material with many superlatives to its name. It is the thinnest known material in the universe and the strongest ever measured. Its charge carriers exhibit giant intrinsic mobility, have zero effective mass, and can travel for micrometers without scattering at room temperature. Graphene can sustain current densities six orders of magnitude higher than that of copper, shows record thermal conductivity and stiffness, is impermeable to gases, and reconciles such conflicting qualities as brittleness and ductility. Electron transport in graphene is described by a Dirac-like equation, which allows the investigation of relativistic quantum phenomena in a benchtop experiment. This review analyzes recent trends in graphene research and applications, and attempts to identify future directions in which the field is likely to develop.

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Evolution. Uniting alignments and trees.

Publication Date: 2009 Jun 19 PMID: 19541988
Authors: Loytynoja, A. - Goldman, N.
Journal: Science

MeSH Categories: Computational Biology, DNA, Evolution, Molecular, *Phylogeny, *Sequence Alignment

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Neuroscience. Bridging the gap and staying local.

Publication Date: 2009 Jun 19 PMID: 19541987
Authors: Korte, M.
Journal: Science

MeSH Categories: Animals, Aplysia, Biological Transport, Memory/*physiology, Neuropeptides/genetics, Protein Biosynthesis, RNA, Messenger/metabolism, Synapses/*physiology

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Chemistry. Extracting potentials from spectra.

Publication Date: 2009 Jun 19 PMID: 19541986
Authors: Bernath, P. F.
Journal: Science

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Immunology. A chronic need for IL-21.

Publication Date: 2009 Jun 19 PMID: 19541985
Authors: Johnson, L. D. - Jameson, S. C.
Journal: Science

MeSH Categories: Animals, CD4-Positive T-Lymphocytes/*immunology, Chronic Disease, Interleukins/*immunology, Mice, Virus Diseases/*immunology

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Ecology. Thriving in salt.

Publication Date: 2009 Jun 19 PMID: 19541984
Authors: Boetius, A. - Joye, S.
Journal: Science

MeSH Categories: Adaptation, Physiological, Algae, Green/physiology, Animals, Artemia/physiology, *Ecosystem, Halobacteriaceae/physiology, *Salinity, Salts, Sodium Chloride, *Water Microbiology

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Chemistry. Squeezing the water out of HCl(aq).

Publication Date: 2009 Jun 19 PMID: 19541983
Authors: Zwier, T. S.
Journal: Science

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Microbiology. No place too cold.

Publication Date: 2009 Jun 19 PMID: 19541982
Authors: Laybourn-Parry, J.
Journal: Science

MeSH Categories: Antarctic Regions, Arctic Regions, Biodiversity, Carbon/metabolism, *Cold Temperature, *Ecosystem, *Water Microbiology

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Agriculture. Nutrient imbalances in agricultural development.

Publication Date: 2009 Jun 19 PMID: 19541981
Authors: Vitousek, P. M. - Naylor, R. - Crews, T. - David, M. B. - Drinkwater, L. E. - Holland, E. - Johnes, P. J. - Katzenberger, J. - Martinelli, L. A. - Matson, P. A. - Nziguheba, G. - Ojima, D. - Palm, C. A. - Robertson, G. P. - Sanchez, P. A. - Townsend, A. R. - Zhang, F. S.
Journal: Science

MeSH Categories: *Agriculture/methods, China, Environmental Pollution, Fertilizers, Kenya, Nitrogen, Phosphorus, *Soil, United States, *Zea mays/growth & development

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Comment on "Experimental test of self-shielding in vacuum ultraviolet photodissociation of CO".

Publication Date: 2009 Jun 19 PMID: 19541980
Authors: Lyons, J. R. - Lewis, R. S. - Clayton, R. N.
Journal: Science

Chakraborty et al. (Reports, 5 September 2008, p. 1328) demonstrated very large, wavelength-dependent mass-independent isotopic effects during carbon monoxide (CO) photodissociation and argued that self-shielding in CO was not responsible. We suggest that variations in band oscillator strengths and linewidths among CO isotopologs are responsible for most of the wavelength dependence observed and that the reported experiments confirm the importance of self-shielding during CO photodissociation.

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Comment on "Experimental test of self-shielding in vacuum ultraviolet photodissociation of CO".

Publication Date: 2009 Jun 19 PMID: 19541979
Authors: Federman, S. R. - Young, E. D.
Journal: Science

Chakraborty et al. (Reports, 5 September 2008, p. 1328) suggested that experimental results provide support for CO photodissociation having caused the oxygen isotope ratio associated with the early solar nebula. We point out that further analysis is required before other mechanisms, such as self-shielding, are shown to be of little importance.

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Comment on "Experimental test of self-shielding in vacuum ultraviolet photodissociation of CO".

Publication Date: 2009 Jun 19 PMID: 19541978
Authors: Yin, Q. Z. - Shi, X. - Chang, C. - Ng, C. Y.
Journal: Science

Chakraborty et al. (Reports, 5 September 2008, p. 1328) concluded that an anomalously enriched atomic oxygen reservoir can be generated through carbon monoxide photodissociation without self-shielding. We show that this conclusion is based on the incorrect assumption that the spectral shifts of the 97.03-nanometers and 107.61-nanometers vibrational bands for C16O, C17O, and C18O are negligible and point out shortcomings of the low-resolution light source used in their experiments.

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Too much quantification hinders creativity.

Publication Date: 2009 Jun 19 PMID: 19541977
Authors: Gurkiewicz, M. - Korngreen, A.
Journal: Science

MeSH Categories: Authorship, *Creativeness, Evaluation Studies as Topic, Information Storage and Retrieval, *Names, Publishing, Science

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Livestock genomics in developing countries.

Publication Date: 2009 Jun 19 PMID: 19541976
Authors: Boettcher, P. J. - Hoffmann, I.
Journal: Science

MeSH Categories: Adaptation, Physiological, Animals, Breeding, Cattle/*genetics, *Developing Countries, Environment, Genetic Variation, *Genomics

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Machines fall short of revolutionary science.

Publication Date: 2009 Jun 19 PMID: 19541975
Authors: Anderson, P. W. - Abrahams, E.
Journal: Science

MeSH Categories: *Artificial Intelligence, Automation, *Science

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Venezuelan science at risk.

Publication Date: 2009 Jun 19 PMID: 19541974
Authors: Bifano, C.
Journal: Science

MeSH Categories: Politics, *Science/trends, Universities/economics/trends, Venezuela

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Cataloguing names the old-fashioned way.

Publication Date: 2009 Jun 19 PMID: 19541973
Authors: Beall, J.
Journal: Science

MeSH Categories: Algorithms, *Cataloging, Information Storage and Retrieval, *Names

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Physics. Is quantum mechanics tried, true, wildly successful, and wrong?

Publication Date: 2009 Jun 19 PMID: 19541972
Authors: Folger, T.
Journal: Science

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Economic recovery. ISO ... 3.5 million U.S. jobs.

Publication Date: 2009 Jun 19 PMID: 19541971
Authors: Holden, C.
Journal: Science

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China. Radio astronomers go for high gain with mammoth telescope.

Publication Date: 2009 Jun 19 PMID: 19541970
Authors: Hvistendahl, M.
Journal: Science

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Genetics. The promise of a cure: 20 years and counting.

Publication Date: 2009 Jun 19 PMID: 19541969
Authors: Couzin-Frankel, J.
Journal: Science

MeSH Categories: Adult, Animals, Child, Preschool, Cystic Fibrosis/*genetics/history/*therapy, Cystic Fibrosis Transmembrane Conductance Regulator/genetics, Gene Therapy/history, History, 20th Century, History, 21st Century, Humans, Male

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American Astronomical Society 214th meeting, 7-11 June 2009, Pasadena, California. Dark-matter model multiplies mass of galactic black holes.

Publication Date: 2009 Jun 19 PMID: 19541968
Authors: Bhattacharjee, Y.
Journal: Science

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American Astronomical Society 214th meeting, 7-11 June 2009, Pasadena, California. Star studies yield better yardsticks.

Publication Date: 2009 Jun 19 PMID: 19541967
Authors: Bhattacharjee, Y.
Journal: Science

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Europe. Italy's MIT grows, and so does controversy over it.

Publication Date: 2009 Jun 19 PMID: 19541966
Authors: Margottini, L.
Journal: Science

MeSH Categories: *Academies and Institutes/economics, Financing, Government, Italy, Nanotechnology, Neurosciences, Research Support as Topic, Robotics

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Law of the sea. A final push to divvy up the sea by all the rules.

Publication Date: 2009 Jun 19 PMID: 19541964
Authors: Kerr, R. A.
Journal: Science

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China. After outcry, government backpedals over internet-filtering software.

Publication Date: 2009 Jun 19 PMID: 19541963
Authors: Xin, H.
Journal: Science

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Arms control. Verification experts puzzled over North Korea's nuclear test.

Publication Date: 2009 Jun 19 PMID: 19541962
Authors: Clery, D.
Journal: Science

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U.S. STEM education. Report calls for grassroots but comprehensive changes.

Publication Date: 2009 Jun 19 PMID: 19541960
Authors: Mervis, J.
Journal: Science

MeSH Categories: Engineering/*education, Faculty, *Mathematics, Science/*education, Technology/*education, United States

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Public health. Expanded U.S. drug agency to control tobacco.

Publication Date: 2009 Jun 19 PMID: 19541959
Authors: Couzin-Frankel, J. - Koenig, R.
Journal: Science

MeSH Categories: *Tobacco, Tobacco Industry, United States, *United States Food and Drug Administration

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Swine flu. After delays, WHO agrees: the 2009 pandemic has begun.

Publication Date: 2009 Jun 19 PMID: 19541958
Authors: Cohen, J. - Enserink, M.
Journal: Science

MeSH Categories: *Disease Outbreaks, Health Services Accessibility, Humans, *Influenza A Virus, H1N1 Subtype, Influenza Vaccines, Influenza, Human/*epidemiology, Politics, World Health, World Health Organization

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Science journalism goes global.

Publication Date: 2009 Jun 19 PMID: 19541957
Authors: Russell, C.
Journal: Science

MeSH Categories: Career Choice, Internationality, *Journalism/economics/trends, *Science, Technology

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Functional Amyloids as Natural Storage of Peptide Hormones in Pituitary Secretory Granules.

Publication Date: 2009 Jun 18 PMID: 19541956
Authors: Maji, S. K. - Perrin, M. H. - Sawaya, M. R. - Jessberger, S. - Vadodaria, K. - Rissman, R. A. - Singru, P. S. - Nilsson, K. P. - Simon, R. - Schubert, D. - Eisenberg, D. - Rivier, J. - Sawchenko, P. - Vale, W. - Riek, R.
Journal: Science

Amyloids are highly organized cross beta-sheet-rich protein or peptide aggregates that are associated with pathological conditions including Alzheimer's disease and type II diabetes. However, amyloids may also have a normal biological function as demonstrated by fungal prions, which are involved in prion replication, and the amyloid protein Pmel17, which is involved in mammalian skin pigmentation. Here, we show that peptide and protein hormones in secretory granules of the endocrine system are stored in an amyloid-like cross beta-sheet-rich conformation. Thus, in contrast to the original association of amyloids with diseases, functional amyloids in the pituitary and other organs can contribute to normal cell and tissue physiology.

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Penumbral Structure and Outflows in Simulated Sunspots.

Publication Date: 2009 Jun 18 PMID: 19541955
Authors: Rempel, M. - Schussler, M. - Cameron, R. H. - Knolker, M.
Journal: Science

Sunspots are concentrations of magnetic field on the visible solar surface that strongly affect the convective energy transport in their interior and surroundings. The filamentary outer regions (penumbrae) of sunspots show systematic radial outward flows along channels of nearly horizontal magnetic field. These flows were discovered 100 years ago and are present in all fully developed sunspots. Using a comprehensive numerical simulation of a sunspot pair, we show that penumbral structures with such outflows form when the average magnetic field inclination to the vertical exceeds about 45 degrees. The systematic outflows are a component of the convective flows that provide the upward energy transport and result from anisotropy introduced by the presence of the inclined magnetic field.

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Translocator Protein (18 kD) as Target for Anxiolytics Without Benzodiazepine-Like Side Effects.

Publication Date: 2009 Jun 18 PMID: 19541954
Authors: Rupprecht, R. - Rammes, G. - Eser, D. - Baghai, T. C. - Schule, C. - Nothdurfter, C. - Troxler, T. - Gentsch, C. - Kalkman, H. O. - Chaperon, F. - Uzunov, V. - McAllister, K. H. - Bertaina-Anglade, V. - La Rochelle, C. D. - Tuerck, D. - Floesser, A. - Kiese, B. - Schumacher, M. - Landgraf, R. - Holsboer, F. - Kucher, K.
Journal: Science

Most antianxiety drugs (anxiolytics) work by modulating neurotransmitters in the brain. Benzodiazepines are fast and effective anxiolytic drugs; however, their long-term use is limited by development of tolerance and withdrawal symptoms. Ligands of the translocator protein (18 kD) may promote the synthesis of endogenous neurosteroids, which also exert anxiolytic effects in animal models. Here, we found that the translocator protein (18 kD) ligand XBD173 enhanced GABAergic neurotransmission and counteracted induced panic attacks in rodents in the absence of sedation and tolerance development. XBD173 also exerted antipanic activity in humans and, in contrast to benzodiazepines, did not cause sedation and withdrawal symptoms. Thus, translocator protein (18 kD) ligands are promising candidates for fast-acting anxiolytic drugs with less severe side effects than benzodiazepines.

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Successful Conservation of a Threatened Maculinea Butterfly.

Publication Date: 2009 Jul 3 PMID: 19541953
Authors: Thomas, J. A. - Simcox, D. J. - Clarke, R. T.
Journal: Science

Globally threatened butterflies have prompted research-based approaches to insect conservation. Here, we describe the reversal of the decline of Maculinea arion (Large Blue), a charismatic specialist whose larvae parasitize Myrmica ant societies. M. arion larvae were more specialized than had previously been recognized, being adapted to a single host-ant species that inhabits a narrow niche in grassland. Inconspicuous changes in grazing and vegetation structure caused host ants to be replaced by similar but unsuitable congeners, explaining the extinction of European Maculinea populations. Once this problem was identified, UK ecosystems were perturbed appropriately, validating models predicting the recovery and subsequent dynamics of the butterfly and ants at 78 sites. The successful identification and reversal of the problem provides a paradigm for other insect conservation projects.

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Consistency Between Satellite-Derived and Modeled Estimates of the Direct Aerosol Effect.

Publication Date: 2009 Jun 18 PMID: 19541952
Authors: Myhre, G.
Journal: Science

The direct aerosol effect has a radiative forcing estimate of -0.5 Wm(-2) in the IPCC AR4, offsetting the warming from CO2 by almost one-third. The uncertainty range, however, ranges from -0.9 to -0.1 Wm(-2), largely due to differences between estimates from global aerosol models and observation-based estimates, with the latter tending to have stronger (more negative) radiative forcing. This study demonstrates consistency between a global aerosol model and adjustment to an observational-based method, giving a global and annual mean radiative forcing weaker than -0.5 Wm(-2) with a best estimate of -0.3 Wm(-2). The physical explanation for the earlier discrepancy is that the relative increase in anthropogenic black carbon (absorbing aerosols) is much larger than the overall increase in the anthropogenic abundance of aerosols.

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Hyper-recombination, diversity, and antibiotic resistance in pneumococcus.

Publication Date: 2009 Jun 12 PMID: 19520963
Authors: Hanage, W. P. - Fraser, C. - Tang, J. - Connor, T. R. - Corander, J.
Journal: Science

Streptococcus pneumoniae is a pathogen of global importance that frequently transfers genetic material between strains and on occasion across species boundaries. In an analysis of 1930 pneumococcal genotypes from six housekeeping genes and 94 genotypes from related species, we identified mosaic genotypes representing admixture between populations and found that these were significantly associated with resistance to several classes of antibiotics. We hypothesize that these observations result from a history of hyper-recombination, which means that these strains are more likely to acquire both divergent genetic material and resistance determinants. This could have consequences for the reemergence of drug resistance after pneumococcal vaccination and also for our understanding of diversification and speciation in recombinogenic bacteria.

MeSH Categories: Alleles, Anti-Bacterial Agents/*pharmacology, Bacterial Typing Techniques, Bayes Theorem, Drug Resistance, Bacterial/*genetics, Genes, Bacterial, *Genetic Variation, Genotype, Pneumococcal Vaccines, *Recombination, Genetic, Sequence Analysis, DNA, Streptococcus pneumoniae/classification/*drug effects/*genetics

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Genome-wide demethylation of Arabidopsis endosperm.

Publication Date: 2009 Jun 12 PMID: 19520962
Authors: Hsieh, T. F. - Ibarra, C. A. - Silva, P. - Zemach, A. - Eshed-Williams, L. - Fischer, R. L. - Zilberman, D.
Journal: Science

Parent-of-origin-specific (imprinted) gene expression is regulated in Arabidopsis thaliana endosperm by cytosine demethylation of the maternal genome mediated by the DNA glycosylase DEMETER, but the extent of the methylation changes is not known. Here, we show that virtually the entire endosperm genome is demethylated, coupled with extensive local non-CG hypermethylation of small interfering RNA-targeted sequences. Mutation of DEMETER partially restores endosperm CG methylation to levels found in other tissues, indicating that CG demethylation is specific to maternal sequences. Endosperm demethylation is accompanied by CHH hypermethylation of embryo transposable elements. Our findings demonstrate extensive reconfiguration of the endosperm methylation landscape that likely reinforces transposon silencing in the embryo.

MeSH Categories: Arabidopsis/*embryology/*genetics/growth & development, Arabidopsis Proteins/genetics/metabolism, *DNA Methylation, *DNA Transposable Elements, DNA, Plant/genetics/metabolism, Gene Expression Regulation, Plant, Gene Silencing, Genes, Plant, *Genome, Plant, *Genomic Imprinting, N-Glycosyl Hydrolases/genetics/metabolism, RNA Interference, RNA, Small Interfering/genetics/metabolism, Repetitive Sequences, Nucleic Acid, Seeds/*genetics/growth & development, Trans-Activators/genetics/metabolism, Transcription Initiation Site

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Extensive demethylation of repetitive elements during seed development underlies gene imprinting.

Publication Date: 2009 Jun 12 PMID: 19520961
Authors: Gehring, M. - Bubb, K. L. - Henikoff, S.
Journal: Science

DNA methylation is an epigenetic mark associated with transposable element silencing and gene imprinting in flowering plants and mammals. In plants, imprinting occurs in the endosperm, which nourishes the embryo during seed development. We have profiled Arabidopsis DNA methylation genome-wide in the embryo and endosperm and found that large-scale methylation changes accompany endosperm development and endosperm-specific gene expression. Transposable element fragments are extensively demethylated in the endosperm. We discovered new imprinted genes by the identification of candidates associated with regions of reduced endosperm methylation and preferential expression in endosperm relative to other parts of the plant. These data suggest that imprinting in plants evolved from targeted methylation of transposable element insertions near genic regulatory elements followed by positive selection when the resulting expression change was advantageous.

MeSH Categories: Alleles, Arabidopsis/*embryology/*genetics/growth & development, Crosses, Genetic, *DNA Methylation, *DNA Transposable Elements, DNA, Plant/genetics/metabolism, Epigenesis, Genetic, Gene Expression Regulation, Developmental, Gene Expression Regulation, Plant, Genes, Plant, Genome, Plant, *Genomic Imprinting, *Repetitive Sequences, Nucleic Acid, Seeds/*genetics/growth & development, Selection (Genetics)

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Structure of rotavirus outer-layer protein VP7 bound with a neutralizing Fab.

Publication Date: 2009 Jun 12 PMID: 19520960
Authors: Aoki, S. T. - Settembre, E. C. - Trask, S. D. - Greenberg, H. B. - Harrison, S. C. - Dormitzer, P. R.
Journal: Science

Rotavirus outer-layer protein VP7 is a principal target of protective antibodies. Removal of free calcium ions (Ca2+) dissociates VP7 trimers into monomers, releasing VP7 from the virion, and initiates penetration-inducing conformational changes in the other outer-layer protein, VP4. We report the crystal structure at 3.4 angstrom resolution of VP7 bound with the Fab fragment of a neutralizing monoclonal antibody. The Fab binds across the outer surface of the intersubunit contact, which contains two Ca2+ sites. Mutations that escape neutralization by other antibodies suggest that the same region bears the epitopes of most neutralizing antibodies. The monovalent Fab is sufficient to neutralize infectivity. We propose that neutralizing antibodies against VP7 act by stabilizing the trimer, thereby inhibiting the uncoating trigger for VP4 rearrangement. A disulfide-linked trimer is a potential subunit immunogen.

MeSH Categories: Amino Acid Sequence, Antibodies, Monoclonal/chemistry/immunology/metabolism, Antibodies, Viral/chemistry/*immunology/metabolism, Antigens, Viral/*chemistry/genetics/*immunology/metabolism, Binding Sites, Binding Sites, Antibody, Calcium/metabolism, Capsid Proteins/*chemistry/genetics/*immunology/metabolism, Crystallography, X-Ray, Epitopes/immunology, Immunoglobulin Fab Fragments/chemistry/*immunology/metabolism, Models, Molecular, Molecular Sequence Data, Mutation, Neutralization Tests, Protein Folding, Protein Multimerization, Protein Structure, Tertiary, Protein Subunits, Recombinant Proteins/chemistry, Rotavirus/*chemistry/immunology, Serotyping

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Leading-edge vortices elevate lift of autorotating plant seeds.

Publication Date: 2009 Jun 12 PMID: 19520959
Authors: Lentink, D. - Dickson, W. B. - van Leeuwen, J. L. - Dickinson, M. H.
Journal: Science

As they descend, the autorotating seeds of maples and some other trees generate unexpectedly high lift, but how they attain this elevated performance is unknown. To elucidate the mechanisms responsible, we measured the three-dimensional flow around dynamically scaled models of maple and hornbeam seeds. Our results indicate that these seeds attain high lift by generating a stable leading-edge vortex (LEV) as they descend. The compact LEV, which we verified on real specimens, allows maple seeds to remain in the air more effectively than do a variety of nonautorotating seeds. LEVs also explain the high lift generated by hovering insects, bats, and possibly birds, suggesting that the use of LEVs represents a convergent aerodynamic solution in the evolution of flight performance in both animals and plants.

MeSH Categories: *Acer, *Betulaceae, Biomechanics, Models, Anatomic, *Movement, Rotation, Seeds/anatomy & histology/*physiology

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Boom-and-bust development patterns across the Amazon deforestation frontier.

Publication Date: 2009 Jun 12 PMID: 19520958
Authors: Rodrigues, A. S. - Ewers, R. M. - Parry, L. - Souza, C. Jr - Verissimo, A. - Balmford, A.
Journal: Science

The Brazilian Amazon is globally important for biodiversity, climate, and geochemical cycles, but is also among the least developed regions in Brazil. Economic development is often pursued through forest conversion for cattle ranching and agriculture, mediated by logging. However, on the basis of an assessment of 286 municipalities in different stages of deforestation, we found a boom-and-bust pattern in levels of human development across the deforestation frontier. Relative standards of living, literacy, and life expectancy increase as deforestation begins but then decline as the frontier evolves, so that pre- and postfrontier levels of human development are similarly low. New financial incentives and policies are creating opportunities for a more sustained development trajectory that is not based on the depletion of nature and ecosystem services.

MeSH Categories: Agriculture, Brazil, *Cities, *Conservation of Natural Resources, Ecosystem, *Educational Status, Humans, Income, *Life Expectancy, Population Dynamics, *Socioeconomic Factors

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Oxygen-18 of O2 records the impact of abrupt climate change on the terrestrial biosphere.

Publication Date: 2009 Jun 12 PMID: 19520957
Authors: Severinghaus, J. P. - Beaudette, R. - Headly, M. A. - Taylor, K. - Brook, E. J.
Journal: Science

Photosynthesis and respiration occur widely on Earth's surface, and the 18O/16O ratio of the oxygen produced and consumed varies with climatic conditions. As a consequence, the history of climate is reflected in the deviation of the 18O/16O of air (delta18Oatm) from seawater delta18O (known as the Dole effect). We report variations in delta18Oatm over the past 60,000 years related to Heinrich and Dansgaard-Oeschger events, two modes of abrupt climate change observed during the last ice age. Correlations with cave records support the hypothesis that the Dole effect is primarily governed by the strength of the Asian and North African monsoons and confirm that widespread changes in low-latitude terrestrial rainfall accompanied abrupt climate change. The rapid delta18Oatm changes can also be used to synchronize ice records by providing global time markers.

MeSH Categories: Antarctic Regions, Atmosphere/*chemistry, *Climatic Processes, *Ecosystem, Ice Cover/*chemistry, Oxygen/*analysis, Oxygen Isotopes/*analysis, Photosynthesis, Rain, Seawater/chemistry, Time

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Measuring the charge state of an adatom with noncontact atomic force microscopy.

Publication Date: 2009 Jun 12 PMID: 19520956
Authors: Gross, L. - Mohn, F. - Liljeroth, P. - Repp, J. - Giessibl, F. J. - Meyer, G.
Journal: Science

Charge states of atoms can be investigated with scanning tunneling microscopy, but this method requires a conducting substrate. We investigated the charge-switching of individual adsorbed gold and silver atoms (adatoms) on ultrathin NaCl films on Cu(111) using a qPlus tuning fork atomic force microscope (AFM) operated at 5 kelvin with oscillation amplitudes in the subangstrom regime. Charging of a gold atom by one electron charge increases the force on the AFM tip by a few piconewtons. Moreover, the local contact potential difference is shifted depending on the sign of the charge and allows the discrimination of positively charged, neutral, and negatively charged atoms. The combination of single-electron charge sensitivity and atomic lateral resolution should foster investigations of molecular electronics, photonics, catalysis, and solar photoconversion.

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Isotopic homojunction band engineering from diamond.

Publication Date: 2009 Jun 12 PMID: 19520955
Authors: Watanabe, H. - Nebel, C. E. - Shikata, S.
Journal: Science

Confinement of charge carriers in semiconductors by quantum wells is usually accomplished with layers that vary in elemental composition, such as aluminum gallium arsenide and gallium arsenide. We fabricated diamond superlattices by creating multilayer structures of isotopically pure carbon isotopes carbon-12 (12C) and carbon-13 (13C), which confine electrons by a difference in band-gap energy of 17 millielectron volts. Cathodoluminescence experiments performed at 80 kelvin showed that excitonic recombination in the higher-energy band of 13C vanishes in favor of increased recombination in the lower-energy 12C material. Carrier confinement was achieved in diamond superlattices made up of both thinner (30 nanometers) and thicker (up to 350 nanometers) layers.

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Polarization control of electron tunneling into ferroelectric surfaces.

Publication Date: 2009 Jun 12 PMID: 19520954
Authors: Maksymovych, P. - Jesse, S. - Yu, P. - Ramesh, R. - Baddorf, A. P. - Kalinin, S. V.
Journal: Science

We demonstrate a highly reproducible control of local electron transport through a ferroelectric oxide via its spontaneous polarization. Electrons are injected from the tip of an atomic force microscope into a thin film of lead-zirconate titanate, Pb(Zr0.2Ti0.8)O3, in the regime of electron tunneling assisted by a high electric field (Fowler-Nordheim tunneling). The tunneling current exhibits a pronounced hysteresis with abrupt switching events that coincide, within experimental resolution, with the local switching of ferroelectric polarization. The large spontaneous polarization of the PZT film results in up to 500-fold amplification of the tunneling current upon ferroelectric switching. The magnitude of the effect is subject to electrostatic control via ferroelectric switching, suggesting possible applications in ultrahigh-density data storage and spintronics.

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Colloidal nanocrystals with molecular metal chalcogenide surface ligands.

Publication Date: 2009 Jun 12 PMID: 19520953
Authors: Kovalenko, M. V. - Scheele, M. - Talapin, D. V.
Journal: Science

Similar to the way that atoms bond to form molecules and crystalline structures, colloidal nanocrystals can be combined together to form larger assemblies. The properties of these structures are determined by the properties of individual nanocrystals and by their interactions. The insulating nature of organic ligands typically used in nanocrystal synthesis results in very poor interparticle coupling. We found that various molecular metal chalcogenide complexes can serve as convenient ligands for colloidal nanocrystals and nanowires. These ligands can be converted into semiconducting phases upon gentle heat treatment, generating inorganic nanocrystal solids. The utility of the inorganic ligands is demonstrated for model systems, including highly conductive arrays of gold nanocrystals capped with Sn2S6(4-) ions and field-effect transistors on cadmium selenide nanocrystals.

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Magnetic fields in the formation of massive stars.

Publication Date: 2009 Jun 12 PMID: 19520952
Authors: Girart, J. M. - Beltran, M. T. - Zhang, Q. - Rao, R. - Estalella, R.
Journal: Science

Massive stars play a crucial role in the production of heavy elements and in the evolution of the interstellar medium, yet how they form is still a matter of debate. We report high-angular-resolution submillimeter observations toward the massive hot molecular core (HMC) in the high-mass star-forming region G31.41+0.31. We find that the evolution of the gravitational collapse of the HMC is controlled by the magnetic field. The HMC is simultaneously contracting and rotating, and the magnetic field lines threading the HMC are deformed along its major axis, acquiring an hourglass shape. The magnetic energy dominates over the centrifugal and turbulence energies, and there is evidence of magnetic braking in the contracting core.

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Herapathite.

Publication Date: 2009 Jun 12 PMID: 19520951
Authors: Kahr, B. - Freudenthal, J. - Phillips, S. - Kaminsky, W.
Journal: Science

Herapathite crystals were first prepared when an assistant to the toxicologist Herapath mixed iodine with the urine of a quinine-fed dog. Herapath was shocked when his transparent crystals sitting one atop the other at right angles were "black as midnight" and predicted that they would replace costly mineral polarizers. Such a change in practice in optics had to await Land, who oriented fragile herapathite microcrystals in extruded polymers, a process that produced the first large-aperture light polarizers and, in turn, the Polaroid empire. Curiously, the crystal structure of herapathite has never been established, and thus its chromophore and mechanism of action remain a mystery. The single crystal structure of herapathite is herein established, and its complete dichroism can be attributed to delocalized excitations along ...I3-...I3-... chains. The workings of herapathite, one of the most successful serendipitously engineered crystals, is only now understood.

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Comprehensive control of atomic motion.

Publication Date: 2009 Jun 12 PMID: 19520950
Authors: Raizen, M. G.
Journal: Science

Recent work provides a general two-step solution to trapping and cooling of atoms. The first step is magnetic stopping of paramagnetic atoms with the use of a sequence of pulsed fields. The second step is single-photon cooling, which is based on a one-way barrier. This cooling method is related intimately to the historic problem of "Maxwell's Demon" and subsequent work by L. Szilard. Here, I discuss the connections between single-photon cooling and information entropy. I also outline future application of these methods to fundamental tests with hydrogen isotopes.

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Materials science. Yield stress fluids slowly yield to analysis.

Publication Date: 2009 Jun 12 PMID: 19520949
Authors: Bonn, D. - Denn, M. M.
Journal: Science

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Cancer. Breaching the cancer fortress.

Publication Date: 2009 Jun 12 PMID: 19520948
Authors: Olson, P. - Hanahan, D.
Journal: Science

MeSH Categories: Animals, Antimetabolites, Antineoplastic/administration & dosage/therapeutic use, *Antineoplastic Combined Chemotherapy Protocols, Carcinoma, Pancreatic Ductal/blood supply/*drug, therapy/metabolism/*pathology, Deoxycytidine/administration & dosage/*analogs & derivatives/therapeutic, use, Disease Models, Animal, Fibroblasts/pathology, Hedgehog Proteins/antagonists & inhibitors/metabolism, Humans, Mice, Neoplasm Metastasis, Neoplasm Transplantation, Neovascularization, Pathologic, Pancreatic Neoplasms/blood supply/*drug therapy/metabolism/*pathology, Signal Transduction/drug effects, Stromal Cells/drug effects/pathology

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Materials science. Silicon carbide as a platform for power electronics.

Publication Date: 2009 Jun 12 PMID: 19520947
Authors: Eddy, C. R. Jr - Gaskill, D. K.
Journal: Science

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Applied physics. Novel probes for molecular electronics.

Publication Date: 2009 Jun 12 PMID: 19520946
Authors: Meyer, E. - Glatzel, T.
Journal: Science

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Astronomy. Extreme spinning tops.

Publication Date: 2009 Jun 12 PMID: 19520945
Authors: Kramer, M.
Journal: Science

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Drug discovery. Repurposing with a difference.

Publication Date: 2009 Jun 12 PMID: 19520944
Authors: Boguski, M. S. - Mandl, K. D. - Sukhatme, V. P.
Journal: Science

MeSH Categories: Drug Discovery/*methods, Humans, Internet, Patents as Topic, *Patient Participation, *Prescription Drugs, *Product Surveillance, Postmarketing, *Technology, Pharmaceutical

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Comment on "Tail reconnection triggering substorm onset".

Publication Date: 2009 Jun 12 PMID: 19520943
Authors: Lui, A. T.
Journal: Science

Angelopoulos et al. (Research Articles, 15 August 2008, p. 931) reported that magnetic reconnection in Earth's magnetotail triggered the onset of a magnetospheric substorm. We provide evidence that (i) near-Earth current disruption, occurring before the conventional tail reconnection signatures, triggered the onset; (ii) the observed auroral intensification and tail reconnection are not causally linked; and (iii) the onset they identified is a continuation of earlier substorm activities.

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Wood energy: the dangers of combustion.

Publication Date: 2009 Jun 12 PMID: 19520942
Authors: Ries, F. J. - Marshall, J. D. - Brauer, M.
Journal: Science

MeSH Categories: *Air Pollution, *Energy-Generating Resources, *Fires, *Wood

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Redesigning the wildlife trade system.

Publication Date: 2009 Jun 12 PMID: 19520940
Authors: Pernetta, A. P.
Journal: Science

MeSH Categories: Animals, *Animals, Wild, *Commerce/legislation & jurisprudence, *International Cooperation

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Wood energy: predicting costs.

Publication Date: 2009 Jun 12 PMID: 19520939
Authors: Doty, F. D.
Journal: Science

MeSH Categories: Costs and Cost Analysis, Energy-Generating Resources/*economics, Fossil Fuels/economics, United States, Wood/*economics

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Wood energy: protect local ecosystems.

Publication Date: 2009 Jun 12 PMID: 19520938
Authors: Titus, B. D. - Maynard, D. G. - Dymond, C. C. - Stinson, G. - Kurz, W. A.
Journal: Science

MeSH Categories: Biomass, *Ecosystem, *Energy-Generating Resources, European Union, *Trees, United States, *Wood

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U.S. higher education. Minority retention rates in science are sore spot for most universities.

Publication Date: 2009 Jun 12 PMID: 19520937
Authors: Koenig, R.
Journal: Science

MeSH Categories: Biological Science Disciplines/*education, California, Humans, Maryland, Mentors, Minority Groups/*education, Program Evaluation, Science/*education, *Students, United States, *Universities/economics

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U.S. higher education. Following the leaders.

Publication Date: 2009 Jun 12 PMID: 19520936
Authors: Koenig, R.
Journal: Science

MeSH Categories: Biological Science Disciplines/*education, Humans, Science/*education, *Students, United States, *Universities, *Vulnerable Populations

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Evolution. Authors scramble to make textbooks conform to Texas science standards.

Publication Date: 2009 Jun 12 PMID: 19520935
Authors: Bhattacharjee, Y.
Journal: Science

MeSH Categories: Biology/*education, Education/standards, *Evolution, Religion and Science, Texas, Textbooks as Topic/*standards

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Profile: Artur Chilingarov. Russia's polar hero.

Publication Date: 2009 Jun 12 PMID: 19520934
Authors: Parfitt, T.
Journal: Science

MeSH Categories: Arctic Regions, Cold Climate, Expeditions, History, 20th Century, History, 21st Century, Ice Cover, Internationality, Oceanography/*history, Politics, Russia

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Profile: Artur Chilingarov. Diving into the sacred sea.

Publication Date: 2009 Jun 12 PMID: 19520933
Authors: Parfitt, T.
Journal: Science

MeSH Categories: Animals, Biodiversity, Climatic Processes, *Ecosystem, *Expeditions, *Fresh Water, Siberia

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Diseases. A medical mystery in middle China.

Publication Date: 2009 Jun 12 PMID: 19520932
Authors: Stone, R.
Journal: Science

MeSH Categories: *Cartilage Diseases/epidemiology/etiology/prevention & control/therapy, China/epidemiology, Chondrocytes/pathology, Endemic Diseases, Free Radicals/metabolism, Genetic Predisposition to Disease, Humans, Incidence, Iodine/deficiency, *Joint Diseases/epidemiology/etiology/prevention & control/therapy, Mycotoxins/toxicity, *Osteoarthritis/epidemiology/etiology/prevention & control/therapy, Selenium/deficiency, Virus Diseases/complications, Water Supply

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Immigration policy. U.S. promises to reduce delays in granting visas for scientists.

Publication Date: 2009 Jun 12 PMID: 19520931
Authors: Bhattacharjee, Y.
Journal: Science

MeSH Categories: Emigration and Immigration, *Foreign Professional Personnel, Humans, *Research Personnel, *Students, *Travel, United States

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Plant breeding. Scientists seek easier access to seed banks.

Publication Date: 2009 Jun 12 PMID: 19520929
Authors: Finkel, E.
Journal: Science

MeSH Categories: Agriculture/economics, Biodiversity, *Breeding, Crops, Agricultural/*genetics, Developing Countries, *International Cooperation, Plants/*genetics, *Seeds

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Japan. Science windfall stimulates high hopes--and political maneuvering.

Publication Date: 2009 Jun 12 PMID: 19520928
Authors: Normile, D.
Journal: Science

MeSH Categories: *Financing, Government/legislation & jurisprudence, Japan, *Politics, *Research Support as Topic/legislation & jurisprudence, *Science

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Patents. U.S. Supreme Court delves into what is and isn't patentable.

Publication Date: 2009 Jun 12 PMID: 19520926
Authors: Marshall, E.
Journal: Science

MeSH Categories: Biotechnology/*legislation & jurisprudence, Commerce/*legislation & jurisprudence, Patents as Topic/*legislation & jurisprudence, *Supreme Court Decisions, United States

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Environmental science. Macau launches late bid to cure its Pearl River Delta blues.

Publication Date: 2009 Jun 12 PMID: 19520925
Authors: Stone, R.
Journal: Science

MeSH Categories: Air Pollution, Animals, Birds, *Conservation of Natural Resources, *Environmental Pollution, Macau, Noise, *Wetlands

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U.S. climate policy. Congress takes first step toward one-stop shopping for climate.

Publication Date: 2009 Jun 12 PMID: 19520924
Authors: Stokstad, E.
Journal: Science

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Reset cooperation with Russia.

Publication Date: 2009 Jun 12 PMID: 19520923
Authors: Schweitzer, G.
Journal: Science

MeSH Categories: *International Cooperation, *National Academy of Sciences (U.S.), *Organizations, Russia, *Science, *Technology, United States

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LXR Regulates Cholesterol Uptake Through Idol-Dependent Ubiquitination of the LDL Receptor.

Publication Date: 2009 Jul 3 PMID: 19520913
Authors: Zelcer, N. - Hong, C. - Boyadjian, R. - Tontonoz, P.
Journal: Science

Cellular cholesterol levels reflect a balance between uptake, efflux, and endogenous synthesis. Here we show that the sterol-responsive nuclear liver X receptor (LXR) helps maintain cholesterol homeostasis, not only through promotion of cholesterol efflux but also through suppression of low-density lipoprotein (LDL) uptake. LXR inhibits the LDL receptor (LDLR) pathway through transcriptional induction of Idol (inducible degrader of the LDLR), an E3 ubiquitin ligase that triggers ubiquitination of the LDLR on its cytoplasmic domain, thereby targeting it for degradation. LXR ligand reduces, whereas LXR knockout increases, LDLR protein levels in vivo in a tissue-selective manner. Idol knockdown in hepatocytes increases LDLR protein levels and promotes LDL uptake. Conversely, adenovirus-mediated expression of Idol in mouse liver promotes LDLR degradation and elevates plasma LDL levels. The LXR-Idol-LDLR axis defines a complementary pathway to sterol response element-binding proteins for sterol regulation of cholesterol uptake.

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Experimental Realization of a Three-Dimensional Topological Insulator, Bi2Te3.

Publication Date: 2009 Jun 11 PMID: 19520912
Authors: Chen, Y. L. - Analytis, J. G. - Chu, J. H. - Liu, Z. K. - Mo, S. K. - Qi, X. L. - Zhang, H. J. - Lu, D. H. - Dai, X. - Fang, Z. - Zhang, S. C. - Fisher, I. R. - Hussain, Z. - Shen, Z. X.
Journal: Science

Three-dimensional topological insulators are a new state of quantum matter with a bulk gap and odd number of relativistic Dirac fermions on the surface. By investigating the surface state of Bi2Te3 with angle resolved photoemission spectroscopy, we demonstrate that the surface state consists of a single nondegenerate Dirac cone. Furthermore, with appropriate hole-doping, the Fermi level can be tuned to intersect only the surface states, indicating a full energy gap for the bulk states. Our results establish that Bi2Te3 is a simple model system for the three-dimensional topological insulator with a single Dirac cone on the surface. The large bulk gap of Bi2Te3 also points to great potential for possible high-temperature spintronics applications.

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Genome-Wide RNAi Screen Identifies Genes Involved in Intestinal Pathogenic Bacterial Infection.

Publication Date: 2009 Jun 11 PMID: 19520911
Authors: Cronin, S. J. - Nehme, N. T. - Limmer, S. - Liegeois, S. - Pospisilik, J. A. - Schramek, D. - Leibbrandt, A. - Simoes, R. D. - Gruber, S. - Puc, U. - Ebersberger, I. - Zoranovic, T. - Neely, G. G. - von Haeseler, A. - Ferrandon, D. - Penninger, J. M.
Journal: Science

Innate immunity represents the first line of defense in animals. We report a genome-wide in vivo Drosophila RNA interference screen to uncover genes involved in susceptibility or resistance to intestinal infection with the bacterium Serratia marcescens. We employed first whole-organism gene suppression followed by tissue-specific silencing in gut epithelium or hemocytes to identify several hundred genes involved in intestinal antibacterial immunity. Among the pathways identified, we showed that the JAK-STAT signaling pathway controls host defense in the gut by regulating stem cell proliferation and thus epithelial cell homeostasis. Thus, we revealed multiple genes involved in antibacterial defense and the regulation of innate immunity.

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Meningococcal Type IV Pili Recruit the Polarity Complex to Cross the Brain Endothelium.

Publication Date: 2009 Jul 3 PMID: 19520910
Authors: Coureuil, M. - Mikaty, G. - Miller, F. - Lecuyer, H. - Bernard, C. - Bourdoulous, S. - Dumenil, G. - Mege, R. M. - Weksler, B. B. - Romero, I. A. - Couraud, P. O. - Nassif, X.
Journal: Science

Type IV pili mediate the initial interaction of many bacterial pathogens with their host cells. In Neisseria meningitidis, the causative agent of cerebrospinal meningitis, type IV pili-mediated adhesion to brain endothelial cells is required for bacteria to cross the blood-brain barrier. Here, type IV pili-mediated adhesion of N. meningitidis to human brain endothelial cells was found to recruit the Par3/Par6/PKCzeta polarity complex that plays a pivotal role in the establishment of eukaryotic cell polarity and the formation of intercellular junctions. This recruitment leads to the formation of ectopic intercellular junctional domains at the site of bacteria-host cell interaction and a subsequent depletion of junctional proteins at the cell-cell interface with opening of the intercellular junctions of the brain-endothelial interface.

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Self-Assembling Sequence-Adaptive Peptide Nucleic Acids.

Publication Date: 2009 Jul 3 PMID: 19520909
Authors: Ura, Y. - Beierle, J. M. - Leman, L. J. - Orgel, L. E. - Ghadiri, M. R.
Journal: Science

Several classes of nucleic acid analogs have been reported, but no synthetic informational polymer has yet proven responsive to selection pressures under enzyme-free conditions. Here, we introduce an oligomer family that efficiently self-assembles by means of reversible covalent anchoring of nucleobase recognition units onto simple oligo-dipeptide backbones [thioester peptide nucleic acids (tPNAs)] and undergoes dynamic sequence modification in response to changing templates in solution. The oligomers specifically self-pair with complementary tPNA strands and cross-pair with RNA and DNA in Watson-Crick fashion. Thus, tPNA combines base-pairing interactions with the side-chain functionalities of typical peptides and proteins. These characteristics might prove advantageous for the design or selection of catalytic constructs or biomaterials that are capable of dynamic sequence repair and adaptation.

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Endogenous activation patterns of Cdc42 GTPase within Drosophila embryos.

Publication Date: 2009 Jun 5 PMID: 19498173
Authors: Kamiyama, D. - Chiba, A.
Journal: Science

Knowing when and where a given protein is activated within intact animals assists in elucidating its in vivo function. With the use of a genetically encoded A-probe (activation bioprobe), we revealed that Cdc42 guanosine triphosphatase (GTPase) remains inactive within Drosophila embryos during the first two-thirds of embryogenesis. Within the central nervous system where Cdc42 activity first becomes up-regulated, individual neurons display patterns restricted to specific subcellular compartments. At both organismal and cellular levels, Cdc42's endogenous activation patterns in the wild type allow predictions of where loss-of-function phenotypes will emerge in cdc42/cdc42 mutants. Genetic tests support the importance of suppressing endogenous Cdc42 activities until needed. Thus, bioprobe-assisted analysis uncovers how ubiquitously expressed signaling proteins control cellular events through continual regulation of their activities within animals.

MeSH Categories: Animals, Axons/ultrastructure, Central Nervous System/embryology/enzymology, Dendrites/ultrastructure, Drosophila/*embryology/enzymology/genetics, Drosophila Proteins/genetics/*metabolism, Embryo, Nonmammalian/*enzymology, Embryonic Development, Enzyme Activation, Fluorescence Resonance Energy Transfer, Molecular Probe Techniques, Motor Neurons/cytology/*enzymology, Mutation, Organogenesis, Phenotype, cdc42 GTP-Binding Protein/genetics/*metabolism

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Halofuginone inhibits TH17 cell differentiation by activating the amino acid starvation response.

Publication Date: 2009 Jun 5 PMID: 19498172
Authors: Sundrud, M. S. - Koralov, S. B. - Feuerer, M. - Calado, D. P. - Kozhaya, A. E. - Rhule-Smith, A. - Lefebvre, R. E. - Unutmaz, D. - Mazitschek, R. - Waldner, H. - Whitman, M. - Keller, T. - Rao, A.
Journal: Science

A central challenge for improving autoimmune therapy is preventing inflammatory pathology without inducing generalized immunosuppression. T helper 17 (TH17) cells, characterized by their production of interleukin-17, have emerged as important and broad mediators of autoimmunity. Here we show that the small molecule halofuginone (HF) selectively inhibits mouse and human TH17 differentiation by activating a cytoprotective signaling pathway, the amino acid starvation response (AAR). Inhibition of TH17 differentiation by HF is rescued by the addition of excess amino acids and is mimicked by AAR activation after selective amino acid depletion. HF also induces the AAR in vivo and protects mice from TH17-associated experimental autoimmune encephalomyelitis. These results indicate that the AAR pathway is a potent and selective regulator of inflammatory T cell differentiation in vivo.

MeSH Categories: Activating Transcription Factor 4/metabolism, Amino Acids/*metabolism/pharmacology, Animals, Autoimmunity/drug effects, Cell Differentiation/drug effects, Cytokines/metabolism, Encephalomyelitis, Autoimmune, Experimental/drug therapy/immunology, Eukaryotic Initiation Factor-2/metabolism, Gene Expression, Humans, Interleukin-17/biosynthesis/genetics, Lymphopoiesis/drug effects, Mice, Mice, Inbred C57BL, Phosphorylation, Piperidines/*pharmacology/therapeutic use, Protein-Serine-Threonine Kinases/metabolism, Quinazolinones/*pharmacology/therapeutic use, Signal Transduction, T-Lymphocyte Subsets/cytology/*drug effects/immunology/metabolism, T-Lymphocytes, Helper-Inducer/cytology/*drug effects/immunology/metabolism

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Mechanoenzymatic cleavage of the ultralarge vascular protein von Willebrand factor.

Publication Date: 2009 Jun 5 PMID: 19498171
Authors: Zhang, X. - Halvorsen, K. - Zhang, C. Z. - Wong, W. P. - Springer, T. A.
Journal: Science

Von Willebrand factor (VWF) is secreted as ultralarge multimers that are cleaved in the A2 domain by the metalloprotease ADAMTS13 to give smaller multimers. Cleaved VWF is activated by hydrodynamic forces found in arteriolar bleeding to promote hemostasis, whereas uncleaved VWF is activated at lower, physiologic shear stresses and causes thrombosis. Single-molecule experiments demonstrate that elongational forces in the range experienced by VWF in the vasculature unfold the A2 domain, and only the unfolded A2 domain is cleaved by ADAMTS13. In shear flow, tensile force on a VWF multimer increases with the square of multimer length and is highest at the middle, providing an efficient mechanism for homeostatic regulation of VWF size distribution by force-induced A2 unfolding and cleavage by ADAMTS13, as well as providing a counterbalance for VWF-mediated platelet aggregation.

MeSH Categories: ADAM Proteins/*metabolism, Binding Sites, Blood Coagulation/physiology, *Hemostasis, Humans, Kinetics, *Mechanical Phenomena, Optical Tweezers, Platelet Aggregation, Protein Conformation, Protein Folding, Protein Multimerization, Protein Structure, Tertiary, Stress, Mechanical, Thermodynamics, von Willebrand Factor/*chemistry/*metabolism

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Rhes, a striatal specific protein, mediates mutant-huntingtin cytotoxicity.

Publication Date: 2009 Jun 5 PMID: 19498170
Authors: Subramaniam, S. - Sixt, K. M. - Barrow, R. - Snyder, S. H.
Journal: Science

Huntington's disease (HD) is caused by a polyglutamine repeat in the protein huntingtin (Htt) with mutant Htt (mHtt) expressed throughout the body and similarly in all brain regions. Yet, HD neuropathology is largely restricted to the corpus striatum. We report that the small guanine nucleotide-binding protein Rhes, which is localized very selectively to the striatum, binds physiologically to mHtt. Using cultured cells, we found Rhes induces sumoylation of mHtt, which leads to cytotoxicity. Thus, Rhes-mHtt interactions can account for the localized neuropathology of HD.

MeSH Categories: Animals, *Cell Death, Cell Line, Cell Survival, Corpus Striatum/metabolism, GTP-Binding Proteins/*metabolism, Humans, Mice, Mice, Transgenic, Mutant Proteins/metabolism, Nerve Tissue Proteins/chemistry/*metabolism, Nuclear Proteins/chemistry/*metabolism, PC12 Cells, RNA Interference, Rats, Recombinant Fusion Proteins/metabolism, SUMO-1 Protein/genetics/metabolism, Small Ubiquitin-Related Modifier Proteins/metabolism, Substrate Specificity

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McsB is a protein arginine kinase that phosphorylates and inhibits the heat-shock regulator CtsR.

Publication Date: 2009 Jun 5 PMID: 19498169
Authors: Fuhrmann, J. - Schmidt, A. - Spiess, S. - Lehner, A. - Turgay, K. - Mechtler, K. - Charpentier, E. - Clausen, T.
Journal: Science

All living organisms face a variety of environmental stresses that cause the misfolding and aggregation of proteins. To eliminate damaged proteins, cells developed highly efficient stress response and protein quality control systems. We performed a biochemical and structural analysis of the bacterial CtsR/McsB stress response. The crystal structure of the CtsR repressor, in complex with DNA, pinpointed key residues important for high-affinity binding to the promoter regions of heat-shock genes. Moreover, biochemical characterization of McsB revealed that McsB specifically phosphorylates arginine residues in the DNA binding domain of CtsR, thereby impairing its function as a repressor of stress response genes. Identification of the CtsR/McsB arginine phospho-switch expands the repertoire of possible protein modifications involved in prokaryotic and eukaryotic transcriptional regulation.

MeSH Categories: Amino Acid Sequence, Arginine/metabolism, Bacillus stearothermophilus/genetics/*metabolism, Bacterial Proteins/*antagonists &, inhibitors/chemistry/genetics/*metabolism, Crystallography, X-Ray, DNA, Bacterial/metabolism, Electrophoretic Mobility Shift Assay, Gene Expression Regulation, Bacterial, Heat-Shock Response/*genetics, Helix-Turn-Helix Motifs, Models, Molecular, Molecular Sequence Data, Mutagenesis, Site-Directed, Phosphorylation, Promoter Regions, Genetic, Protein Kinases/chemistry/genetics/*metabolism, Protein Structure, Tertiary, Repressor Proteins/*antagonists &, inhibitors/chemistry/genetics/*metabolism, Tandem Mass Spectrometry

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Epigenetic temporal control of mouse Hox genes in vivo.

Publication Date: 2009 Jun 5 PMID: 19498168
Authors: Soshnikova, N. - Duboule, D.
Journal: Science

During vertebrate development, the temporal control of Hox gene transcriptional activation follows the genomic order of the genes within the Hox clusters. Although it is recognized that this "Hox clock" serves to coordinate body patterning, the underlying mechanism remains elusive. We have shown that successive Hox gene activation in the mouse embryo is closely associated with a directional transition in chromatin status, as judged by the dynamic progression of transcription-competent modifications: Increases in activation marks correspond to decreases in repressive marks. Furthermore, using a mouse in which a Hox cluster was split into two pieces, we document the necessity to maintain a clustered organization to properly implement this process. These results suggest that chromatin modifications are important parameters in the temporal regulation of this gene family.

MeSH Categories: Acetylation, Animals, Body Patterning, Chromatin/*metabolism, Embryo, Mammalian/*physiology, *Embryonic Development, *Epigenesis, Genetic, Gene Expression Profiling, *Gene Expression Regulation, Developmental, *Genes, Homeobox, Histones/metabolism, Methylation, Mice, Multigene Family, RNA Polymerase II/metabolism, Transcription, Genetic, *Transcriptional Activation

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Social transmission of a host defense against cuckoo parasitism.

Publication Date: 2009 Jun 5 PMID: 19498167
Authors: Davies, N. B. - Welbergen, J. A.
Journal: Science

Coevolutionary arms races between brood parasites and hosts involve genetic adaptations and counter-adaptations. However, hosts sometimes acquire defenses too rapidly to reflect genetic change. Our field experiments show that observation of cuckoo (Cuculus canorus) mobbing by neighbors on adjacent territories induced reed warblers (Acrocephalus scirpaceus) to increase the mobbing of cuckoos but not of parrots (a harmless control) on their own territory. In contrast, observation of neighbors mobbing parrots had no effect on reed warblers' responses to either cuckoos or parrots. These results indicate that social learning provides a mechanism by which hosts rapidly increase their nest defense against brood parasites. Such enemy-specific social transmission enables hosts to track fine-scale spatiotemporal variation in parasitism and may influence the coevolutionary trajectories and population dynamics of brood parasites and hosts.

MeSH Categories: Animals, *Behavior, Animal, *Birds, Female, Great Britain, Learning, Male, *Nesting Behavior, Parrots, Social Behavior, *Songbirds, Territoriality, Vocalization, Animal

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Observation of single colloidal platinum nanocrystal growth trajectories.

Publication Date: 2009 Jun 5 PMID: 19498166
Authors: Zheng, H. - Smith, R. K. - Jun, Y. W. - Kisielowski, C. - Dahmen, U. - Alivisatos, A. P.
Journal: Science

Understanding of colloidal nanocrystal growth mechanisms is essential for the syntheses of nanocrystals with desired physical properties. The classical model for the growth of monodisperse nanocrystals assumes a discrete nucleation stage followed by growth via monomer attachment, but has overlooked particle-particle interactions. Recent studies have suggested that interactions between particles play an important role. Using in situ transmission electron microscopy, we show that platinum nanocrystals can grow either by monomer attachment from solution or by particle coalescence. Through the combination of these two processes, an initially broad size distribution can spontaneously narrow into a nearly monodisperse distribution. We suggest that colloidal nanocrystals take different pathways of growth based on their size- and morphology-dependent internal energies.

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Natural quasicrystals.

Publication Date: 2009 Jun 5 PMID: 19498165
Authors: Bindi, L. - Steinhardt, P. J. - Yao, N. - Lu, P. J.
Journal: Science

Quasicrystals are solids whose atomic arrangements have symmetries that are forbidden for periodic crystals, including configurations with fivefold symmetry. All examples identified to date have been synthesized in the laboratory under controlled conditions. Here we present evidence of a naturally occurring icosahedral quasicrystal that includes six distinct fivefold symmetry axes. The mineral, an alloy of aluminum, copper, and iron, occurs as micrometer-sized grains associated with crystalline khatyrkite and cupalite in samples reported to have come from the Koryak Mountains in Russia. The results suggest that quasicrystals can form and remain stable under geologic conditions, although there remain open questions as to how this mineral formed naturally.

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Late Pleistocene demography and the appearance of modern human behavior.

Publication Date: 2009 Jun 5 PMID: 19498164
Authors: Powell, A. - Shennan, S. - Thomas, M. G.
Journal: Science

The origins of modern human behavior are marked by increased symbolic and technological complexity in the archaeological record. In western Eurasia this transition, the Upper Paleolithic, occurred about 45,000 years ago, but many of its features appear transiently in southern Africa about 45,000 years earlier. We show that demography is a major determinant in the maintenance of cultural complexity and that variation in regional subpopulation density and/or migratory activity results in spatial structuring of cultural skill accumulation. Genetic estimates of regional population size over time show that densities in early Upper Paleolithic Europe were similar to those in sub-Saharan Africa when modern behavior first appeared. Demographic factors can thus explain geographic variation in the timing of the first appearance of modern behavior without invoking increased cognitive capacity.

MeSH Categories: Africa, Anthropology, Cultural, Archaeology, Asia, *Cultural Evolution, Emigration and Immigration, Europe, Evolution, Humans, Middle East, Models, Theoretical, *Population Density, Population Dynamics, *Social Behavior, Time

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Did warfare among ancestral hunter-gatherers affect the evolution of human social behaviors?

Publication Date: 2009 Jun 5 PMID: 19498163
Authors: Bowles, S.
Journal: Science

Since Darwin, intergroup hostilities have figured prominently in explanations of the evolution of human social behavior. Yet whether ancestral humans were largely "peaceful" or "warlike" remains controversial. I ask a more precise question: If more cooperative groups were more likely to prevail in conflicts with other groups, was the level of intergroup violence sufficient to influence the evolution of human social behavior? Using a model of the evolutionary impact of between-group competition and a new data set that combines archaeological evidence on causes of death during the Late Pleistocene and early Holocene with ethnographic and historical reports on hunter-gatherer populations, I find that the estimated level of mortality in intergroup conflicts would have had substantial effects, allowing the proliferation of group-beneficial behaviors that were quite costly to the individual altruist.

MeSH Categories: *Altruism, Anthropology, Cultural, Archaeology, Cooperative Behavior, *Cultural Evolution, *Evolution, Female, Genetic Variation, Humans, Male, Microsatellite Repeats, Models, Theoretical, *Social Behavior, *War

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Regulation of hypoxia-inducible factor 2alpha signaling by the stress-responsive deacetylase sirtuin 1.

Publication Date: 2009 Jun 5 PMID: 19498162
Authors: Dioum, E. M. - Chen, R. - Alexander, M. S. - Zhang, Q. - Hogg, R. T. - Gerard, R. D. - Garcia, J. A.
Journal: Science

To survive in hostile environments, organisms activate stress-responsive transcriptional regulators that coordinately increase production of protective factors. Hypoxia changes cellular metabolism and thus activates redox-sensitive as well as oxygen-dependent signal transducers. We demonstrate that Sirtuin 1 (Sirt1), a redox-sensing deacetylase, selectively stimulates activity of the transcription factor hypoxia-inducible factor 2 alpha (HIF-2alpha) during hypoxia. The effect of Sirt1 on HIF-2alpha required direct interaction of the proteins and intact deacetylase activity of Sirt1. Select lysine residues in HIF-2alpha that are acetylated during hypoxia confer repression of Sirt1 augmentation by small-molecule inhibitors. In cultured cells and mice, decreasing or increasing Sirt1 activity or levels affected expression of the HIF-2alpha target gene erythropoietin accordingly. Thus, Sirt1 promotes HIF-2 signaling during hypoxia and likely other environmental stresses.

MeSH Categories: Acetylation, Amino Acid Substitution, Animals, Basic Helix-Loop-Helix Transcription, Factors/chemistry/genetics/*metabolism, *Cell Hypoxia, Cell Line, Cell Line, Tumor, Erythropoietin/genetics, Gene Expression Regulation, Humans, Kidney/metabolism, Liver/embryology/metabolism, Mice, Mice, Knockout, Mutant Proteins/chemistry/metabolism, Oxidation-Reduction, *Signal Transduction, Sirtuins/genetics/*metabolism

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Anthropogenic impacts on nitrogen isotopes of ice-core nitrate.

Publication Date: 2009 Jun 5 PMID: 19498161
Authors: Hastings, M. G. - Jarvis, J. C. - Steig, E. J.
Journal: Science

A strong, unambiguous negative trend is found in the nitrogen isotopic composition (delta15N) of nitrate over the industrial period, on the basis of a 100-meter ice core from Summit, Greenland. This record indicates that ice-core nitrate reflects changes in nitrogen oxide (NOx) source emissions and that anthropogenic emissions of NOx have resulted in a 12 per mil decline in delta15N of atmospheric nitrate from preindustrial values to present. Variations in the isotopic composition of nitrate may affect the interpretation of other records of environmental change that are affected by atmospheric nitrate.

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Disulfide formation in the ER and mitochondria: two solutions to a common process.

Publication Date: 2009 Jun 5 PMID: 19498160
Authors: Riemer, J. - Bulleid, N. - Herrmann, J. M.
Journal: Science

The endoplasmic reticulum (ER) was long considered to be the only compartment of the eukaryotic cell in which protein folding is accompanied by enzyme-catalyzed disulfide bond formation. However, it has recently become evident that cells harbor a second oxidizing compartment, the mitochondrial intermembrane space, where disulfide formation facilitates protein translocation from the cytosol. Moreover, protein oxidation has been implicated in many mitochondria-associated processes central for human health such as apoptosis, aging, and regulation of the respiratory chain. Whereas the machineries of ER and mitochondria both form disulfides between cysteine residues, they do not share evolutionary origins and exhibit distinct mechanistic properties. Here, we summarize the current knowledge of these oxidation systems and discuss their functional similarities and differences.

MeSH Categories: Aging, Animals, Disease, Disulfides/*metabolism, Electron Transport, Endoplasmic Reticulum/*metabolism, Humans, Hydrogen Peroxide/metabolism, Mitochondria/*metabolism, Mitochondrial Membrane Transport Proteins/chemistry/metabolism, Mitochondrial Membranes/*metabolism, Mitochondrial Proteins/chemistry/metabolism, Oxidation-Reduction, Protein Disulfide-Isomerases/chemistry/metabolism, Proteins/chemistry/*metabolism

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Immunology. Amino acid addiction.

Publication Date: 2009 Jun 5 PMID: 19498159
Authors: Blander, J. M. - Amsen, D.
Journal: Science

MeSH Categories: Amino Acids/*metabolism, Animals, Autoimmunity/drug effects, Cell Differentiation/drug effects, Eukaryotic Initiation Factor-2/metabolism, Evolution, Molecular, Gene Expression Regulation/drug effects, Humans, Interleukin-17/biosynthesis, Lymphopoiesis/drug effects, Mice, Multiple Sclerosis/immunology, Phosphorylation, Piperidines/*pharmacology, Protein Biosynthesis, Protein-Serine-Threonine Kinases/metabolism, Quinazolinones/*pharmacology, Signal Transduction/drug effects, T-Lymphocyte Subsets/cytology/*drug effects/immunology/metabolism, T-Lymphocytes, Helper-Inducer/cytology/*drug effects/immunology/metabolism

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Cell biology. Hypoxic hookup.

Publication Date: 2009 Jun 5 PMID: 19498158
Authors: Guarente, L.
Journal: Science

MeSH Categories: Acetylation, Aging, Animals, Basic Helix-Loop-Helix Transcription Factors/*metabolism, *Cell Hypoxia, Cells, Cultured, Erythropoietin/biosynthesis/genetics, Gene Expression, Gene Expression Regulation, Humans, Hypoxia-Inducible Factor 1, alpha Subunit/metabolism, Liver/embryology/metabolism, Mice, NAD/metabolism, Neoplasms/metabolism/pathology, Oxidation-Reduction, Sirtuins/genetics/*metabolism

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Anthropology. On becoming modern.

Publication Date: 2009 Jun 5 PMID: 19498157
Authors: Mace, R.
Journal: Science

MeSH Categories: *Altruism, Anthropology, Cultural, Archaeology, Cooperative Behavior, *Cultural Evolution, *Evolution, Female, Genetic Variation, Humans, Male, Models, Theoretical, *Population Density, *Social Behavior, Time, War

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Biochemistry. Force signaling in biology.

Publication Date: 2009 Jun 5 PMID: 19498156
Authors: Christof, J. - Gebhardt, M. - Rief, M.
Journal: Science

MeSH Categories: ADAM Proteins/*metabolism, Binding Sites, Blood Coagulation/physiology, Hemostasis/*physiology, Humans, *Mechanical Phenomena, Optical Tweezers, Protein Conformation, Protein Folding, Protein Multimerization, Protein Structure, Tertiary, Stress, Mechanical, von Willebrand Factor/*chemistry/*metabolism

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Physics. Dealing with decoherence.

Publication Date: 2009 Jun 5 PMID: 19498155
Authors: Fischer, J. - Loss, D.
Journal: Science

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Materials science. Watching nanocrystals grow.

Publication Date: 2009 Jun 5 PMID: 19498154
Authors: Murray, C. B.
Journal: Science

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Science innovation. Assessing the impact of science funding.

Publication Date: 2009 Jun 5 PMID: 19498153
Authors: Lane, J.
Journal: Science

MeSH Categories: *Diffusion of Innovation, *Economics, Financing, Government/*legislation & jurisprudence, *Public Policy, *Research Support as Topic/legislation & jurisprudence, *Science, United States

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Keeping Mars clean.

Publication Date: 2009 Jun 5 PMID: 19498152
Authors: Kramer, W. R.
Journal: Science

MeSH Categories: *Bacteria, *Exobiology, Extraterrestrial Environment, *Mars, Public Policy, *Space Flight, *Spacecraft

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Life in science. It takes a village.

Publication Date: 2009 Jun 5 PMID: 19498151
Authors: Kosten, S. - Lacerot, G.
Journal: Science

MeSH Categories: Argentina, Ecology, *Wit and Humor as Topic

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Stem cell debate extends to scientists.

Publication Date: 2009 Jun 5 PMID: 19498150
Authors: Boackle, S.
Journal: Science

MeSH Categories: Embryo Research/*legislation & jurisprudence, *Embryonic Stem Cells, Humans, United States

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A step ahead on the HIV collaboratory.

Publication Date: 2009 Jun 5 PMID: 19498149
Authors: Murphy, R. L. - Autran, B. - Katlama, C. - Brucker, G. - Debre, P. - Calvez, V. - Clotet, B. - Clumeck, N. - Costagliola, D. - Deeks, S. G. - Dorrell, L. - Gatell, J. - Haase, A. - Klein, M. - Lazzarin, A. - McMichael, A. J. - Papagno, L. - Schacker, T. W. - Wain-Hobson, S. - Walker, B. D. - Youle, M.
Journal: Science

MeSH Categories: Anti-HIV Agents/*therapeutic use, HIV Infections/*drug therapy/therapy/virology, Humans, Immunologic Factors/*therapeutic use, *International Cooperation

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Astronomy. The tales told by lonely galaxies.

Publication Date: 2009 Jun 5 PMID: 19498148
Authors: Cho, A.
Journal: Science

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The Gonzo Scientist. Results from the science dance match-up challenge.

Publication Date: 2009 Jun 5 PMID: 19498147
Authors: Bohannon, J.
Journal: Science

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Marine biology. Scientists get no respect from fishery managers.

Publication Date: 2009 Jun 5 PMID: 19498146
Authors: Normile, D.
Journal: Science

MeSH Categories: Animals, Conservation of Natural Resources, *Fisheries/statistics & numerical data, International Cooperation, *Tuna

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Marine biology. Persevering researchers make a splash with farm-bred tuna.

Publication Date: 2009 Jun 5 PMID: 19498145
Authors: Normile, D.
Journal: Science

MeSH Categories: Animals, *Breeding, Diet, Female, *Fisheries, Japan, Male, Reproduction, Tuna/*physiology

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Transportation research. Hydrogen cars: fad or the future?

Publication Date: 2009 Jun 5 PMID: 19498144
Authors: Service, R. F.
Journal: Science

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Origins. On the origin of sexual reproduction.

Publication Date: 2009 Jun 5 PMID: 19498143
Authors: Zimmer, C.
Journal: Science

MeSH Categories: Animals, *Evolution, Female, Host-Parasite Interactions, Humans, Male, Mating Preference, Animal, *Meiosis, Models, Biological, Mutation, Recombination, Genetic, *Reproduction, *Sex

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The Biology of Genomes, 5-9 May 2009, Cold Spring Harbor, New York. The bug and the bacterium: interdependent genomes.

Publication Date: 2009 Jun 5 PMID: 19498142
Authors: Pennisi, E.
Journal: Science

MeSH Categories: Amino Acids/biosynthesis, Animals, Aphids/*genetics/*microbiology, Buchnera/*genetics/metabolism, Genes, Bacterial, Genes, Duplicate, Genes, Insect, Genome, Bacterial, *Genome, Insect, Sequence Analysis, DNA, *Symbiosis

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The Biology of Genomes, 5-9 May 2009, Cold Spring Harbor, New York. Water flea boasts whopper gene count.

Publication Date: 2009 Jun 5 PMID: 19498141
Authors:
Journal: Science

MeSH Categories: Adaptation, Biological, Animals, Daphnia/*genetics/physiology, *Genes, Genes, Duplicate, *Genome, Oligonucleotide Array Sequence Analysis, Sequence Analysis, DNA

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The Biology of Genomes, 5-9 May 2009, Cold Spring Harbor, New York. Some RNA may play key role in repressing genes, slowing cancer.

Publication Date: 2009 Jun 5 PMID: 19498140
Authors: Pennisi, E.
Journal: Science

MeSH Categories: Animals, Chromatin Assembly and Disassembly, *Gene Silencing, Genes, p53, Humans, Neoplasms/*genetics, RNA, Untranslated/genetics/metabolism/*physiology, Repressor Proteins/metabolism

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U.S. higher education. Report finds no gender bias in faculty hiring, resources.

Publication Date: 2009 Jun 5 PMID: 19498138
Authors: Mervis, J.
Journal: Science

MeSH Categories: *Career Mobility, Faculty/*statistics & numerical data, Female, Humans, Male, Personnel Selection, *Prejudice, *Research, Universities/manpower/statistics & numerical data

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Newsmaker interview. Eugenie Scott toils in defense of evolution. Interview by Yudhijit Bhattacharjee.

Publication Date: 2009 Jun 5 PMID: 19498137
Authors: Scott, E.
Journal: Science

MeSH Categories: Biology/*education, Education/legislation & jurisprudence, *Evolution, Religion and Science, Teaching, United States

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Geoscience. The Quaternary Period wins out in the end.

Publication Date: 2009 Jun 5 PMID: 19498136
Authors: Kerr, R. A.
Journal: Science

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Research facilities. European neutron source finally finds a home.

Publication Date: 2009 Jun 5 PMID: 19498134
Authors: Clery, D.
Journal: Science

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Particle physics. Chinese scientists hope to make deepest, darkest dreams come true.

Publication Date: 2009 Jun 5 PMID: 19498133
Authors: Normile, D.
Journal: Science

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Science for future physicians.

Publication Date: 2009 Jun 5 PMID: 19498132
Authors: Long, S. - Alpern, R.
Journal: Science

MeSH Categories: *Curriculum, *Education, Medical, Undergraduate, *Education, Premedical, *Educational Measurement, Humans, Natural Science Disciplines/*education

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Amplified trace gas removal in the troposphere.

Publication Date: 2009 Jun 26 PMID: 19498111
Authors: Hofzumahaus, A. - Rohrer, F. - Lu, K. - Bohn, B. - Brauers, T. - Chang, C. C. - Fuchs, H. - Holland, F. - Kita, K. - Kondo, Y. - Li, X. - Lou, S. - Shao, M. - Zeng, L. - Wahner, A. - Zhang, Y.
Journal: Science

The degradation of trace gases and pollutants in the troposphere is dominated by their reaction with hydroxyl radicals (OH). The importance of OH rests on its high reactivity, its ubiquitous photochemical production in the sunlit atmosphere, and most importantly on its regeneration in the oxidation chain of the trace gases. In the current understanding, the recycling of OH proceeds through HO2 reacting with NO, thereby forming ozone. A recent field campaign in the Pearl River Delta, China, quantified tropospheric OH and HO2 concentrations and turnover rates by direct measurements. We report that concentrations of OH were three to five times greater than expected, and we propose the existence of a pathway for the regeneration of OH independent of NO, which amplifies the degradation of pollutants without producing ozone.

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Auxin-dependent patterning and gamete specification in the Arabidopsis female gametophyte.

Publication Date: 2009 Jun 26 PMID: 19498110
Authors: Pagnussat, G. C. - Alandete-Saez, M. - Bowman, J. L. - Sundaresan, V.
Journal: Science

The female reproductive unit of flowering plants, the haploid female gametophyte, is highly reduced relative to other land plants. We show that patterning of the Arabidopsis female gametophyte depends on an asymmetric distribution of the hormone auxin during its syncitial development. Furthermore, this auxin gradient is correlated with location-specific auxin biosynthesis, rather than auxin efflux that directs patterning in the diploid sporophytic tissues comprising the rest of the plant. Manipulation of auxin responses or synthesis induces switching of gametic and nongametic cell identities and specialized nonreproductive cells to exhibit attributes presumptively lost during angiosperm evolution. These findings may account for the unique egg cell specification characteristic of angiosperms and the formation of seeds with single diploid embryos while containing endosperm that can have variable numbers of parental haploid genomes.

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RIP3, an Energy Metabolism Regulator that Switches TNF-Induced Cell Death from Apoptosis to Necrosis.

Publication Date: 2009 Jun 4 PMID: 19498109
Authors: Zhang, D. W. - Shao, J. - Lin, J. - Zhang, N. - Lu, B. J. - Lin, S. C. - Dong, M. Q. - Han, J.
Journal: Science

Necrosis can be induced by stimulating death receptors with tumor necrosis factor (TNF) or other agonists; however, the underlying mechanism differentiating necrosis from apoptosis is largely unknown. We identified the protein kinase RIP3 as a molecular switch between TNF-induced apoptosis and necrosis in NIH3T3 cells, and found that RIP3 was required for necrosis in other cells. RIP3 did not affect RIP1-mediated apoptosis, but was required for RIP1-mediated necrosis and the enhancement of necrosis by the caspase inhibitor zVAD. By activating key enzymes of metabolic pathways, RIP3 regulated TNF-induced reactive oxygen species production, which partially accounts for RIP3's ability to promote necrosis. Our data suggest that modulation of energy metabolism in response to death stimuli has an important role in the choice between apoptosis and necrosis.

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IRAP Identifies an Endosomal Compartment Required for MHC Class I Cross-Presentation.

Publication Date: 2009 Jun 4 PMID: 19498108
Authors: Saveanu, L. - Carroll, O. - Weimershaus, M. - Guermonprez, P. - Firat, E. - Lindo, V. - Greer, F. - Davoust, J. - Kratzer, R. - Keller, S. R. - Niedermann, G. - van Endert, P.
Journal: Science

Major histocompatibility class (MHC) I molecules present peptides, produced through cytosolic proteasomal degradation of cellular proteins, to cytotoxic T lymphocytes. In dendritic cells, the peptides can also be derived from internalized antigens, in a process known as cross-presentation. The cellular compartments involved in cross-presentation remain poorly defined. Here, we found a role for peptide trimming by insulin-regulated aminopeptidase (IRAP) in cross-presentation. In human dendritic cells, IRAP was localized to a Rab14(+) endosomal storage compartment in which it interacted with MHC class I molecules. IRAP deficiency compromised cross-presentation in vitro and in vivo, but did not effect endogenous presentation. We propose the existence of two pathways for proteasome-dependent cross-presentation in which final peptide trimming involves IRAP in endosomes, and the related aminopeptidases in the endoplasmic reticulum.

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Extending universal nodal excitations optimizes superconductivity in Bi2Sr2CaCu2O8+delta.

Publication Date: 2009 Jun 26 PMID: 19498107
Authors: Pushp, A. - Parker, C. V. - Pasupathy, A. N. - Gomes, K. K. - Ono, S. - Wen, J. - Xu, Z. - Gu, G. - Yazdani, A.
Journal: Science

Understanding the mechanism by which d wave superconductivity in the cuprates emerges and is optimized by doping the Mott insulator is one of the major outstanding problems in condensed-matter physics. Our high-resolution scanning tunneling microscopy measurements of the high-transition temperature (Tc) superconductor Bi2Sr2CaCu2O8+delta show that samples with different Tc values in the low doping regime follow a remarkably universal d wave low-energy excitation spectrum, indicating a doping-independent nodal gap. We demonstrate that Tc instead correlates with the fraction of the Fermi surface over which the samples exhibit the universal spectrum. Optimal Tc is achieved when all parts of the Fermi surface follow this universal behavior. Increasing the temperature above Tc turns the universal spectrum into an arc of gapless excitations, whereas overdoping breaks down the universal nodal behavior.

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Ventral tegmental area BDNF induces an opiate-dependent-like reward state in naive rats.

Publication Date: 2009 Jun 26 PMID: 19478142
Authors: Vargas-Perez, H. - Kee, R. T. - Walton, C. H. - Hansen, D. M. - Razavi, R. - Clarke, L. - Bufalino, M. R. - Allison, D. W. - Steffensen, S. C. - van der Kooy, D.
Journal: Science

The neural mechanisms underlying the transition from a drug-nondependent to a drug-dependent state remain elusive. Chronic exposure to drugs has been shown to increase brain-derived neurotrophic factor (BDNF) levels in ventral tegmental area (VTA) neurons. BDNF infusions into the VTA potentiate several behavioral effects of drugs, including psychomotor sensitization and cue-induced drug seeking. We found that a single infusion of BDNF into the VTA promotes a shift from a dopamine-independent to a dopamine-dependent opiate reward system, identical to that seen when an opiate-naive rat becomes dependent and withdrawn. This shift involves a switch in the gamma-aminobutyric acid type A (GABAA) receptors of VTA GABAergic neurons, from inhibitory to excitatory signaling.

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IL-21R on T cells is critical for sustained functionality and control of chronic viral infection.

Publication Date: 2009 Jun 19 PMID: 19478140
Authors: Frohlich, A. - Kisielow, J. - Schmitz, I. - Freigang, S. - Shamshiev, A. T. - Weber, J. - Marsland, B. J. - Oxenius, A. - Kopf, M.
Journal: Science

Chronic viral infection is often associated with the dysfunction of virus-specific T cells. Our studies using Il21r-deficient (Il21r-/-) mice now suggest that interleukin-21 (IL-21) is critical for the long-term maintenance and functionality of CD8+ T cells and the control of chronic lymphocytic choriomeningitis virus infection in mice. Cell-autonomous IL-21 receptor (IL-21R)-dependent signaling by CD8+ T cells was required for sustained cell proliferation and cytokine production during chronic infection. Il21r-/- mice showed normal CD8+ T cell expansion, effector function, memory homeostasis, and recall responses during acute and after resolved infection with several other nonpersistent viruses. These data suggest that IL-21R signaling is required for the maintenance of polyfunctional T cells during chronic viral infections and have implications for understanding the immune response to other persisting antigens, such as tumors.

MeSH Categories: Animals, CD8-Positive T-Lymphocytes/*immunology, Chronic Disease, Humans, Immunologic Memory, Interferon-gamma/biosynthesis, Lymphocytic Choriomeningitis/*immunology, Mice, Mice, Inbred C57BL, Peptide Fragments/biosynthesis, Receptors, Interleukin-21/*immunology, Signal Transduction

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Structure and mechanism of an amino acid antiporter.

Publication Date: 2009 Jun 19 PMID: 19478139
Authors: Gao, X. - Lu, F. - Zhou, L. - Dang, S. - Sun, L. - Li, X. - Wang, J. - Shi, Y.
Journal: Science

Virulent enteric pathogens such as Escherichia coli strain O157:H7 rely on acid-resistance (AR) systems to survive the acidic environment in the stomach. A major component of AR is an arginine-dependent arginine:agmatine antiporter that expels intracellular protons. Here, we report the crystal structure of AdiC, the arginine:agmatine antiporter from E. coli O157:H7 and a member of the amino acid/polyamine/organocation (APC) superfamily of transporters at 3.6 A resolution. The overall fold is similar to that of several Na+-coupled symporters. AdiC contains 12 transmembrane segments, forms a homodimer, and exists in an outward-facing, open conformation in the crystals. A conserved, acidic pocket opens to the periplasm. Structural and biochemical analysis reveals the essential ligand-binding residues, defines the transport route, and suggests a conserved mechanism for the antiporter activity.

MeSH Categories: Agmatine/metabolism, Amino Acid Sequence, Amino Acid Transport Systems/*chemistry/genetics/metabolism/physiology, Antiporters/*chemistry/genetics/metabolism/physiology, Arginine/metabolism, Conserved Sequence, Crystallography, X-Ray, Escherichia coli O157/*chemistry/genetics/metabolism, Escherichia coli Proteins/*chemistry/genetics/metabolism/physiology, Models, Molecular, Molecular Sequence Data, Protein Conformation

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Inhibition of Hedgehog signaling enhances delivery of chemotherapy in a mouse model of pancreatic cancer.

Publication Date: 2009 Jun 12 PMID: 19460966
Authors: Olive, K. P. - Jacobetz, M. A. - Davidson, C. J. - Gopinathan, A. - McIntyre, D. - Honess, D. - Madhu, B. - Goldgraben, M. A. - Caldwell, M. E. - Allard, D. - Frese, K. K. - Denicola, G. - Feig, C. - Combs, C. - Winter, S. P. - Ireland-Zecchini, H. - Reichelt, S. - Howat, W. J. - Chang, A. - Dhara, M. - Wang, L. - Ruckert, F. - Grutzmann, R. - Pilarsky, C. - Izeradjene, K. - Hingorani, S. R. - Huang, P. - Davies, S. E. - Plunkett, W. - Egorin, M. - Hruban, R. H. - Whitebread, N. - McGovern, K. - Adams, J. - Iacobuzio-Donahue, C. - Griffiths, J. - Tuveson, D. A.
Journal: Science

Pancreatic ductal adenocarcinoma (PDA) is among the most lethal human cancers in part because it is insensitive to many chemotherapeutic drugs. Studying a mouse model of PDA that is refractory to the clinically used drug gemcitabine, we found that the tumors in this model were poorly perfused and poorly vascularized, properties that are shared with human PDA. We tested whether the delivery and efficacy of gemcitabine in the mice could be improved by coadministration of IPI-926, a drug that depletes tumor-associated stromal tissue by inhibition of the Hedgehog cellular signaling pathway. The combination therapy produced a transient increase in intratumoral vascular density and intratumoral concentration of gemcitabine, leading to transient stabilization of disease. Thus, inefficient drug delivery may be an important contributor to chemoresistance in pancreatic cancer.

MeSH Categories: Animals, Antineoplastic Agents/*administration & dosage/metabolism/therapeutic use, *Antineoplastic Combined Chemotherapy Protocols, Apoptosis/drug effects, Carcinoma, Pancreatic Ductal/blood supply/*drug, therapy/metabolism/pathology, Cell Line, Tumor, Cell Proliferation/drug effects, Deoxycytidine/administration & dosage/*analogs &, derivatives/metabolism/therapeutic use, Disease Models, Animal, Drug Resistance, Neoplasm, Hedgehog Proteins/antagonists & inhibitors/*metabolism, Humans, Kruppel-Like Transcription Factors/metabolism, Mice, Neoplasm Transplantation, Neovascularization, Pathologic, Pancreatic Neoplasms/blood supply/*drug therapy/metabolism/pathology, Receptors, G-Protein-Coupled/antagonists & inhibitors/metabolism, Signal Transduction/drug effects, Stromal Cells/drug effects/pathology, Veratrum Alkaloids/*administration & dosage/pharmacokinetics/therapeutic, use

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Germline P granules are liquid droplets that localize by controlled dissolution/condensation.

Publication Date: 2009 Jun 26 PMID: 19460965
Authors: Brangwynne, C. P. - Eckmann, C. R. - Courson, D. S. - Rybarska, A. - Hoege, C. - Gharakhani, J. - Julicher, F. - Hyman, A. A.
Journal: Science

In sexually reproducing organisms, embryos specify germ cells, which ultimately generate sperm and eggs. In Caenorhabditis elegans, the first germ cell is established when RNA and protein-rich P granules localize to the posterior of the one-cell embryo. Localization of P granules and their physical nature remain poorly understood. Here we show that P granules exhibit liquid-like behaviors, including fusion, dripping, and wetting, which we used to estimate their viscosity and surface tension. As with other liquids, P granules rapidly dissolved and condensed. Localization occurred by a biased increase in P granule condensation at the posterior. This process reflects a classic phase transition, in which polarity proteins vary the condensation point across the cell. Such phase transitions may represent a fundamental physicochemical mechanism for structuring the cytoplasm.

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A radio pulsar/x-ray binary link.

Publication Date: 2009 Jun 12 PMID: 19460964
Authors: Archibald, A. M. - Stairs, I. H. - Ransom, S. M. - Kaspi, V. M. - Kondratiev, V. I. - Lorimer, D. R. - McLaughlin, M. A. - Boyles, J. - Hessels, J. W. - Lynch, R. - van Leeuwen, J. - Roberts, M. S. - Jenet, F. - Champion, D. J. - Rosen, R. - Barlow, B. N. - Dunlap, B. H. - Remillard, R. A.
Journal: Science

Radio pulsars with millisecond spin periods are thought to have been spun up by the transfer of matter and angular momentum from a low-mass companion star during an x-ray-emitting phase. The spin periods of the neutron stars in several such low-mass x-ray binary (LMXB) systems have been shown to be in the millisecond regime, but no radio pulsations have been detected. Here we report on detection and follow-up observations of a nearby radio millisecond pulsar (MSP) in a circular binary orbit with an optically identified companion star. Optical observations indicate that an accretion disk was present in this system within the past decade. Our optical data show no evidence that one exists today, suggesting that the radio MSP has turned on after a recent LMXB phase.

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Beryllium dimer--caught in the act of bonding.

Publication Date: 2009 Jun 19 PMID: 19460963
Authors: Merritt, J. M. - Bondybey, V. E. - Heaven, M. C.
Journal: Science

The beryllium dimer is a deceptively simple molecule that, in spite of having only eight electrons, poses difficult challenges for ab initio quantum chemical methods. More than 100 theoretical investigations of the beryllium dimer have been published, reporting a wide range of bond lengths and dissociation energies. In contrast, there have been only a handful of experimental studies that provide data against which these models could be tested. Ultimately, the uncertain extrapolation behavior associated with the available data has prevented quantitative comparisons with theory. In our experiment, we resolve this issue by recording and analyzing spectra that sample all the bound vibrational levels of the beryllium dimer molecule's electronic ground state. After more than 70 years of research on this problem, the experimental data and theoretical models for the dimer are finally reconciled.

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MicroRNA-92a controls angiogenesis and functional recovery of ischemic tissues in mice.

Publication Date: 2009 Jun 26 PMID: 19460962
Authors: Bonauer, A. - Carmona, G. - Iwasaki, M. - Mione, M. - Koyanagi, M. - Fischer, A. - Burchfield, J. - Fox, H. - Doebele, C. - Ohtani, K. - Chavakis, E. - Potente, M. - Tjwa, M. - Urbich, C. - Zeiher, A. M. - Dimmeler, S.
Journal: Science

MicroRNAs (miRs) are small noncoding RNAs that regulate gene expression by binding to target messenger RNAs (mRNAs), leading to translational repression or degradation. Here, we show that the miR-17approximately92 cluster is highly expressed in human endothelial cells and that miR-92a, a component of this cluster, controls the growth of new blood vessels (angiogenesis). Forced overexpression of miR-92a in endothelial cells blocked angiogenesis in vitro and in vivo. In mouse models of limb ischemia and myocardial infarction, systemic administration of an antagomir designed to inhibit miR-92a led to enhanced blood vessel growth and functional recovery of damaged tissue. MiR-92a appears to target mRNAs corresponding to several proangiogenic proteins, including the integrin subunit alpha5. Thus, miR-92a may serve as a valuable therapeutic target in the setting of ischemic disease.

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Diversity and complexity in DNA recognition by transcription factors.

Publication Date: 2009 Jun 26 PMID: 19443739
Authors: Badis, G. - Berger, M. F. - Philippakis, A. A. - Talukder, S. - Gehrke, A. R. - Jaeger, S. A. - Chan, E. T. - Metzler, G. - Vedenko, A. - Chen, X. - Kuznetsov, H. - Wang, C. F. - Coburn, D. - Newburger, D. E. - Morris, Q. - Hughes, T. R. - Bulyk, M. L.
Journal: Science

Sequence preferences of DNA binding proteins are a primary mechanism by which cells interpret the genome. Despite the central importance of these proteins in physiology, development, and evolution, comprehensive DNA binding specificities have been determined experimentally for only a few proteins. Here, we used microarrays containing all 10-base pair sequences to examine the binding specificities of 104 distinct mouse DNA binding proteins representing 22 structural classes. Our results reveal a complex landscape of binding, with virtually every protein analyzed possessing unique preferences. Roughly half of the proteins each recognized multiple distinctly different sequence motifs, challenging our molecular understanding of how proteins interact with their DNA binding sites. This complexity in DNA recognition may be important in gene regulation and in the evolution of transcriptional regulatory networks.

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Pd-Pt bimetallic nanodendrites with high activity for oxygen reduction.

Publication Date: 2009 Jun 5 PMID: 19443738
Authors: Lim, B. - Jiang, M. - Camargo, P. H. - Cho, E. C. - Tao, J. - Lu, X. - Zhu, Y. - Xia, Y.
Journal: Science

Controlling the morphology of Pt nanostructures can provide a great opportunity to improve their catalytic properties and increase their activity on a mass basis. We synthesized Pd-Pt bimetallic nanodendrites consisting of a dense array of Pt branches on a Pd core by reducing K2PtCl4 with L-ascorbic acid in the presence of uniform Pd nanocrystal seeds in an aqueous solution. The Pt branches supported on faceted Pd nanocrystals exhibited relatively large surface areas and particularly active facets toward the oxygen reduction reaction (ORR), the rate-determining step in a proton-exchange membrane fuel cell. The Pd-Pt nanodendrites were two and a half times more active on the basis of equivalent Pt mass for the ORR than the state-of-the-art Pt/C catalyst and five times more active than the first-generation supportless Pt-black catalyst.

MeSH Categories: Catalysis, Electrochemistry, Metal Nanoparticles/*chemistry, Oxidation-Reduction, Oxygen/*chemistry, Palladium/*chemistry, Platinum/*chemistry

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Synapse- and stimulus-specific local translation during long-term neuronal plasticity.

Publication Date: 2009 Jun 19 PMID: 19443737
Authors: Wang, D. O. - Kim, S. M. - Zhao, Y. - Hwang, H. - Miura, S. K. - Sossin, W. S. - Martin, K. C.
Journal: Science

Long-term memory and synaptic plasticity require changes in gene expression and yet can occur in a synapse-specific manner. Messenger RNA localization and regulated translation at synapses are thus critical for establishing synapse specificity. Using live-cell microscopy of photoconvertible fluorescent protein translational reporters, we directly visualized local translation at synapses during long-term facilitation of Aplysia sensory-motor synapses. Translation of the reporter required multiple applications of serotonin, was spatially restricted to stimulated synapses, was transcript- and stimulus-specific, and occurred during long-term facilitation but not during long-term depression of sensory-motor synapses. Translational regulation only occurred in the presence of a chemical synapse and required calcium signaling in the postsynaptic motor neuron. Thus, highly regulated local translation occurs at synapses during long-term plasticity and requires trans-synaptic signals.

MeSH Categories: Animals, Aplysia, Biological Transport, Calcium/physiology, Cells, Cultured, FMRFamide/physiology, Gene Expression Regulation, Genes, Reporter, Luminescent Proteins/genetics, Motor Neurons/physiology, Neuronal Plasticity/genetics/*physiology, Neuropeptides/genetics, Neurotransmitter Agents/genetics, *Protein Biosynthesis, RNA, Messenger/metabolism, Sensory Receptor Cells/physiology, Serotonin/physiology, Synapses/genetics/*physiology

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Determining the dynamics of entanglement.

Publication Date: 2009 Jun 12 PMID: 19443736
Authors: Jimenez Farias, O. - Lombard Latune, C. - Walborn, S. P. - Davidovich, L. - Souto Ribeiro, P. H.
Journal: Science

The estimation of the entanglement of multipartite systems undergoing decoherence is important for assessing the robustness of quantum information processes. It usually requires access to the final state and its full reconstruction through quantum tomography. General dynamical laws may simplify this task. We found that when one of the parties of an initially entangled two-qubit system is subject to a noisy channel, a single universal curve describes the dynamics of entanglement for both pure and mixed states, including those for which entanglement suddenly disappears. Our result, which is experimentally demonstrated using a linear optics setup, leads to a direct and efficient determination of entanglement through the knowledge of the initial state and single-party process tomography alone, foregoing the need to reconstruct the final state.

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A vital role for interleukin-21 in the control of a chronic viral infection.

Publication Date: 2009 Jun 19 PMID: 19443735
Authors: Yi, J. S. - Du, M. - Zajac, A. J.
Journal: Science

Understanding the factors that regulate the induction, quality, and longevity of antiviral T cell responses is essential for devising rational strategies to prevent or combat infections. In this study, we show that interleukin-21 (IL-21), likely produced by CD4+ T cells, directly influences the generation of polyfunctional CD8+ T cells and that the number of CD4+ T cells that produce IL-21 differs markedly between acute and chronic infections. IL-21 regulates the development of CD8+ T cell exhaustion and the ability to contain chronic lymphocytic choriomeningitis virus infection. Thus, IL-21 serves as a critical helper factor that shapes the functional quality of antiviral CD8+ T cells and is required for viral control.

MeSH Categories: Animals, CD4-Positive T-Lymphocytes/*immunology, CD8-Positive T-Lymphocytes/*immunology, Chronic Disease, Interleukins/*immunology, Lymphocytic Choriomeningitis/*immunology, Lymphocytic choriomeningitis virus, Mice, Mice, Inbred C57BL, Viral Load

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Pandemic potential of a strain of influenza A (H1N1): early findings.

Publication Date: 2009 Jun 19 PMID: 19433588
Authors: Fraser, C. - Donnelly, C. A. - Cauchemez, S. - Hanage, W. P. - Van Kerkhove, M. D. - Hollingsworth, T. D. - Griffin, J. - Baggaley, R. F. - Jenkins, H. E. - Lyons, E. J. - Jombart, T. - Hinsley, W. R. - Grassly, N. C. - Balloux, F. - Ghani, A. C. - Ferguson, N. M. - Rambaut, A. - Pybus, O. G. - Lopez-Gatell, H. - Alpuche-Aranda, C. M. - Chapela, I. B. - Zavala, E. P. - Guevara, D. M. - Checchi, F. - Garcia, E. - Hugonnet, S. - Roth, C.
Journal: Science

A novel influenza A (H1N1) virus has spread rapidly across the globe. Judging its pandemic potential is difficult with limited data, but nevertheless essential to inform appropriate health responses. By analyzing the outbreak in Mexico, early data on international spread, and viral genetic diversity, we make an early assessment of transmissibility and severity. Our estimates suggest that 23,000 (range 6000 to 32,000) individuals had been infected in Mexico by late April, giving an estimated case fatality ratio (CFR) of 0.4% (range: 0.3 to 1.8%) based on confirmed and suspected deaths reported to that time. In a community outbreak in the small community of La Gloria, Veracruz, no deaths were attributed to infection, giving an upper 95% bound on CFR of 0.6%. Thus, although substantial uncertainty remains, clinical severity appears less than that seen in the 1918 influenza pandemic but comparable with that seen in the 1957 pandemic. Clinical attack rates in children in La Gloria were twice that in adults (<15 years of age: 61%; >/=15 years: 29%). Three different epidemiological analyses gave basic reproduction number (R0) estimates in the range of 1.4 to 1.6, whereas a genetic analysis gave a central estimate of 1.2. This range of values is consistent with 14 to 73 generations of human-to-human transmission having occurred in Mexico to late April. Transmissibility is therefore substantially higher than that of seasonal flu, and comparable with lower estimates of R0 obtained from previous influenza pandemics.

MeSH Categories: *Disease Outbreaks, Humans, *Influenza A Virus, H5N1 Subtype, Influenza, Human/*epidemiology/mortality/transmission/virology, Mexico/epidemiology, Molecular Sequence Data, Travel, World Health

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Recruitment of an area involved in eye movements during mental arithmetic.

Publication Date: 2009 Jun 19 PMID: 19423779
Authors: Knops, A. - Thirion, B. - Hubbard, E. M. - Michel, V. - Dehaene, S.
Journal: Science

Throughout the history of mathematics, concepts of number and space have been tightly intertwined. We tested the hypothesis that cortical circuits for spatial attention contribute to mental arithmetic in humans. We trained a multivariate classifier algorithm to infer the direction of an eye movement, left or right, from the brain activation measured in the posterior parietal cortex. Without further training, the classifier then generalized to an arithmetic task. Its left versus right classification could be used to sort out subtraction versus addition trials, whether performed with symbols or with sets of dots. These findings are consistent with the suggestion that mental arithmetic co-opts parietal circuitry associated with spatial coding.

MeSH Categories: Adult, Eye Movements/*physiology, Female, Humans, Magnetic Resonance Imaging, Male, *Mathematics, Mental Processes/*physiology, Parietal Lobe/*physiology, Recruitment, Neurophysiological

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Fluorescent false neurotransmitters visualize dopamine release from individual presynaptic terminals.

Publication Date: 2009 Jun 12 PMID: 19423778
Authors: Gubernator, N. G. - Zhang, H. - Staal, R. G. - Mosharov, E. V. - Pereira, D. B. - Yue, M. - Balsanek, V. - Vadola, P. A. - Mukherjee, B. - Edwards, R. H. - Sulzer, D. - Sames, D.
Journal: Science

The nervous system transmits signals between neurons via neurotransmitter release during synaptic vesicle fusion. In order to observe neurotransmitter uptake and release from individual presynaptic terminals directly, we designed fluorescent false neurotransmitters as substrates for the synaptic vesicle monoamine transporter. Using these probes to image dopamine release in the striatum, we made several observations pertinent to synaptic plasticity. We found that the fraction of synaptic vesicles releasing neurotransmitter per stimulus was dependent on the stimulus frequency. A kinetically distinct "reserve" synaptic vesicle population was not observed under these experimental conditions. A frequency-dependent heterogeneity of presynaptic terminals was revealed that was dependent in part on D2 dopamine receptors, indicating a mechanism for frequency-dependent coding of presynaptic selection.

MeSH Categories: Animals, Benz(a)Anthracenes/*metabolism, Cells, Cultured, Chromaffin Cells/*metabolism, Corpus Striatum/cytology/*metabolism, Dopamine/*metabolism, Dopamine Antagonists/pharmacology, Electric Stimulation, Exocytosis, Fluorescent Dyes, Mice, Mice, Transgenic, Neuronal Plasticity, Neurotransmitter Agents/*metabolism, Presynaptic Terminals/*metabolism, Receptors, Dopamine D2/antagonists & inhibitors/metabolism, Sulpiride/pharmacology, Synaptic Vesicles/*metabolism

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IL-21 is required to control chronic viral infection.

Publication Date: 2009 Jun 19 PMID: 19423777
Authors: Elsaesser, H. - Sauer, K. - Brooks, D. G.
Journal: Science

CD4+ and CD8+ T cell functions are rapidly aborted during chronic infection, preventing viral clearance. CD4+ T cell help is required throughout chronic infection so as to sustain CD8+ T cell responses; however, the necessary factor(s) provided by CD4+ T cells are currently unknown. Using a mouse model of chronic viral infection, we demonstrated that interleukin-21 (IL-21) is an essential component of CD4+ T cell help. In the absence of IL-21 signaling, despite elevated CD4+ T cell responses, CD8+ T cell responses are severely impaired. CD8+ T cells directly require IL-21 to avoid deletion, maintain immunity, and resolve persistent infection. Thus, IL-21 specifically sustains CD8+ T cell effector activity and provides a mechanism of CD4+ T cell help during chronic viral infection.

MeSH Categories: Animals, CD4-Positive T-Lymphocytes/*immunology, CD8-Positive T-Lymphocytes/*immunology, Chronic Disease, Interleukins/genetics/*immunology, Lymphocyte Activation, Lymphocyte Depletion, Lymphocytic Choriomeningitis/*immunology, Lymphocytic choriomeningitis virus, Mice, Mice, Inbred C57BL, Mice, Knockout, Signal Transduction, Virus Diseases/*immunology

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Large-area synthesis of high-quality and uniform graphene films on copper foils.

Publication Date: 2009 Jun 5 PMID: 19423775
Authors: Li, X. - Cai, W. - An, J. - Kim, S. - Nah, J. - Yang, D. - Piner, R. - Velamakanni, A. - Jung, I. - Tutuc, E. - Banerjee, S. K. - Colombo, L. - Ruoff, R. S.
Journal: Science

Graphene has been attracting great interest because of its distinctive band structure and physical properties. Today, graphene is limited to small sizes because it is produced mostly by exfoliating graphite. We grew large-area graphene films of the order of centimeters on copper substrates by chemical vapor deposition using methane. The films are predominantly single-layer graphene, with a small percentage (less than 5%) of the area having few layers, and are continuous across copper surface steps and grain boundaries. The low solubility of carbon in copper appears to help make this growth process self-limiting. We also developed graphene film transfer processes to arbitrary substrates, and dual-gated field-effect transistors fabricated on silicon/silicon dioxide substrates showed electron mobilities as high as 4050 square centimeters per volt per second at room temperature.

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Superconductivity at the two-dimensional limit.

Publication Date: 2009 Jun 5 PMID: 19407146
Authors: Qin, S. - Kim, J. - Niu, Q. - Shih, C. K.
Journal: Science

Superconductivity in the extreme two-dimensional limit is studied on ultrathin lead films down to two atomic layers, where only a single channel of quantum well states exists. Scanning tunneling spectroscopy reveals that local superconducting order remains robust until two atomic layers, where the transition temperature abruptly plunges to a lower value, depending sensitively on the exact atomic structure of the film. Our result shows that Cooper pairs can still form in the last two-dimensional channel of electron states, although their binding is strongly affected by the substrate.

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