This Week in Science

Science  12 Feb 2016:
Vol. 351, Issue 6274, pp. 676
  1. Cancer

    Helping cancer cells exit blood vessels

    1. Nancy R. Gough

    Cartoon view of cancer cells (blue) exiting blood vessels to form new metastatic tumors


    Metastasizing cancer cells must migrate into the bloodstream to colonize secondary sites. Locard-Paulet et al. cocultured breast cancer cells with endothelial cells, a system that mimics the early events associated with exit from the bloodstream. The receptor EPHA2 can mediate repulsion between cells. Activation of EPHA2 in breast cancer cells by an endothelial cell ligand was associated with decreased lung colonization in vivo. EPHA2 activation was decreased in a metastatic breast cancer cell line that targets the lung, which in vitro had greater migration rates through endothelial cell monolayers.

    Sci. Signal. 9, ra15 (2016).

  2. Photocatalysis

    Copper's light touch forges C-N bonds

    1. Jake Yeston

    Organic photochemistry has traditionally relied on excitation in the ultraviolet, where carbon-based compounds tend to absorb. Over the past decade, the field has undergone a renaissance as compounds that absorb visible light have proven to be versatile catalysts for organic reactions. For the most part, however, these catalysts have contained rare metals such as ruthenium or iridium. Kainz et al. now report a blue light-driven C-N bond-forming reaction catalyzed by Earth-abundant copper (see the Perspective by Greaney). Through coordination to a chiral ligand, the copper center couples alkyl chlorides to indoles and carbazoles with a high degree of enantioselectivity.

    Science, this issue p. 681; see also p. 666

  3. Transcription

    The SAGA of removing nucleosomal ubiquitin

    1. Guy Riddihough

    Covalent modifications of histones play a critical role in gene regulation. The addition of the small protein ubiquitin to histone H2B in nucleosomes is a mark of actively transcribed chromatin. Morgan et al. determined the crystal structure of a nucleosome bound by a module of the SAGA protein complex that removes ubiquitin from histone H2B (see the Perspective by Workman). The structure suggests that the deubiquitinating module can remove ubiquitin at multiple points during the transcription cycle.

    Science, this issue p. 725; see also p. 667

  4. Human Genomics

    The legacy of human-Neandertal interbreeding

    1. Laura M. Zahn

    Non-African humans are estimated to have inherited on average 1.5 to 4% of their genomes from Neandertals. However, how this genetic legacy affects human traits is unknown. Simonti et al. combined genotyping data with electronic health records. Individual Neandertal alleles were correlated with clinically relevant phenotypes in individuals of European descent. These archaic genetic variants were associated with medical conditions affecting the skin, the blood, and the risk of depression.

    Science, this issue p. 737

  5. Metabolism

    Controlling supplies for DNA and RNA synthesis

    1. L. Bryan Ray

    The mTORC1 protein kinase complex regulates anabolic metabolism and coordinates cellular signals that promote growth with availability of required precursor metabolites. Signaling through mTORC1 controls pyrimidine synthesis. Ben-Sahra et al. found that mTORC1 also functions by a different mechanism to regulate purine biosynthesis, thus generating precursors for the synthesis of RNA and DNA (see the Perspective by Ma and Jones). Signaling by mTORC1 caused accumulation of the transcription factor ATF4, which enhances production of the enzyme methylenetetrahydrofolate dehydrogenase 2, thus leading to increased production of the purine nucleotides needed for cell growth.

    Science, this issue p. 728; see also p. 670

  6. Global Water Cycle

    By land or by sea

    1. H. Jesse Smith

    How much of an effect does terrestrial groundwater storage have on sea-level rise? Reager et al. used gravity measurements made between 2002 and 2014 by NASA's Gravity Recovery And Climate Experiment (GRACE) satellites to quantify variations in groundwater storage. Combining those data with estimates of mass loss by glaciers revealed groundwater's impact on sea-level change. Net groundwater storage has been increasing, and the greatest regional changes, both positive and negative, are associated with climate-driven variability in precipitation. Thus, groundwater storage has slowed the rate of recent sea-level rise by roughly 15%.

    Science, this issue p. 699

  7. Immunology

    An unconventional route to protection

    1. Kristen L. Mueller

    One promising approach toward an HIV-1 vaccine involves infecting people with cytomegalovirus engineered to express proteins from HIV-1. This approach, which works by eliciting virus-killing CD8+ T cells, provides robust protection in nonhuman primate models. Hansen et al. have found out why this approach is so effective. Normally, peptide antigens presented by major histocompatibility complex-1a (MHC-Ia) activate CD8+ T cells. In vaccinated monkeys, however, CD8+ T cells reacted to peptide antigens presented by MHC-E molecules instead. Moreover, MHC-E could present a much wider range of peptides than MHC-Ia.

    Science, this issue p. 714

  8. Astronomy

    How stars grow

    1. Kip Hodges

    Conventional wisdom has long held that young stars grow gradually through the inward migration of mass within their protoplanetary disks. Liu et al. now show that the process may also include violent episodes of especially rapid mass accretion. Although the precise causes of such events are still being studied, the emerging perspective on protoplanetary disk evolution is one that is more dynamic and chaotic than previously believed.

    Sci. Adv. 10.1126.sciadv.00875 (2016).

  9. Carbon Cycle

    Warming making bigger CO2 swings

    1. H. Jesse Smith

    The combined effects of climate change and vegetation dynamics at high northern latitudes have amplified the seasonal variation of atmospheric CO2 concentrations over the past half century. Forkel et al. combined observations and models to show that climate warming has caused the photosynthetic uptake of carbon to increase faster than its respiratory release from the terrestrial biosphere. This has increased the difference from summer to winter, as well as the latitudinal gradient. Because of the physiological limitations to carbon uptake by terrestrial vegetation, this negative feedback to warming in the boreal north and Arctic cannot continue indefinitely.

    Science, this issue p. 696

  10. Gene Regulation

    Parasitic DNAs help and hinder evolution

    1. Guy Riddihough

    Transposable elements are parasitic DNAs that can duplicate themselves and jump around their host genomes. They can both disrupt gene function and drive genome evolution. Elbarbary et al. review the roles of two classes of transposable elements in gene regulation and disease: long interspersed elements (LINEs) and short interspersed elements (SINEs). Roughly a third of the human genome consists of LINEs and SINEs. They contribute to a broad range of important genome and gene regulatory features, while at the same time being responsible for number of human diseases.

    Science, this issue p. 10.1126/science.aac7247

  11. Valleytronics

    Stacking to prolong valley lifetime

    1. Jelena Stajic

    In the material MoSe2, which, like graphene, has a two-dimensional honeycomb crystal lattice, the electronic structure has two “valleys.” Electrons can be distinguished by the valley they reside in, making them act as potential information carriers. However, electrons easily lose this information by scattering into the other valley. Rivera et al. placed single layers of MoSe2 and WSe2 on top of each other and shone circularly polarized light on the structure. The light caused excitons—pairs of electrons and holes—to form so that the hole and electron came from the same valley but different layers. The valley-specific character of such excitons persisted far longer than would be possible in a single layer of either material.

    Science, this issue p. 688

  12. Gene Regulation

    Genetic programming for self-renewal

    1. Kristen L. Mueller

    Instead of repopulating themselves from tissue-resident stem cell pools like most types of differentiated cells, tissue macrophages maintain themselves by self-renewing. The underlying genetic programs that allow for this, however, are unknown. Soucie et al. now report that in macrophages at homeostasis, a pair of transcription factors (MafB and c-Maf) bind to and repress the enhancers of genes regulating self-renewal. When macrophages need to replenish their stocks, for example in response to injury, they transiently decrease MafB and c-Maf expression so they can self-renew. A parallel pathway also operates to control the self-renewal of embryonic stem cells.

    Science, this issue p. 10.1126/science.aad5510

  13. Materials Science

    Flexible power for flexible electronics

    1. Marc S. Lavine

    A challenge for flexible electronics is to couple devices with power sources that are also flexible. Ideally, they could also be processed in a way that is compatible with current microfabrication technologies. Huang et al. deposited a relatively thick layer of TiC on top of an oxide-coated Si film. After chlorination, most, but importantly not all, of the TiC was converted into a porous carbon film that could be turned into an electrochemical capacitor. The carbon films were highly flexible, and the residual TiC acted as a stress buffer with the underlying Si film. The films could be separated from the Si to form free-floating films, with the TiC providing a support layer.

    Science, this issue p. 691

  14. Microbial Physiology

    Long-term partners uncoupled

    1. Nicholas S. Wigginton

    Methane-munching archaea in marine sediments live closely coupled to sulfate-reducing bacteria in a syntrophic relationship. Surprisingly, however, these archaea do not necessarily need their bacterial partners to survive or grow. Scheller et al. performed stable isotope incubation experiments with deep-sea methane seep sediments (see the Perspective by Rotaru and Thamdrup). Several groups of methane-oxidizing archaea could use a range of soluble electron acceptors instead of coupling to active bacterial sulfate reduction. This decoupled pathway shows that methane-oxidizing archaea transfer electrons extracellularly and may even possess the capacity to respire iron and manganese minerals that are abundant in seafloor sediments.

    Science, this issue p. 703; see also p. 658

  15. Lung Physiology

    Neuroendocrine cells as air sensors

    1. Beverly A. Purnell

    Liters of air pass through the lung every minute. Signals in the atmospheric environment are processed into physiological outputs, including the immune response. Branchfield et al. show that rare airway cells called pulmonary neuroendocrine cells (PNECs) sense and respond to airborne cues (see the Perspective by Whitsett and Morrisey). Inactivating Roundabout genes in mouse PNECs prevents normal PNEC clustering and causes an increase in the production of neuropeptides, which in turn trigger a heightened immune response. Thus PNECs, despite their rarity, are sensitive and effective rheostats on the airway wall that receive, interpret, and respond to environmental stimuli.

    Science, this issue p. 707; see also p. 662

  16. Epigenetics

    Quantitative analysis of epigenetic memory

    1. L. Bryan Ray

    To explore quantitative and dynamic properties of transcriptional regulation by epigenetic modifications, Bintu et al. monitored a transcriptional reporter gene carried on a human artificial chromosome in Chinese hamster ovary cells (see the Perspective by Keung and Khalil). They measured effects of DNA methylation and histone modifications by methylation or deacetylation in single cells using time-lapse microscopy. Silencing was an all-or-none, stochastic event, so graded adjustments to transcription occurred from changes in the proportion of cells that responded. Furthermore, the duration of recruitment of the chromatin regulators determined the fraction of cells that were silenced. Thus, distinct modifiers can produce different characteristics of epigenetic memory.

    Science, this issue p. 720; see also p. 661

  17. Autoimmunity

    T cells target peptide combos

    1. Kristen L. Mueller

    One of the enduring mysteries of autoimmunity is the identity of the specific proteins targeted by autoimmune T cells. Delong et al. used mass spectrometry to elucidate the peptide targets of autoimmune T cells isolated from a mouse model of type 1 diabetes. T cells targeted hybrid peptides formed by the covalent linking of a peptide derived from pro-insulin to other peptides derived from proteins found in pancreatic beta cells. T cells isolated from the pancreatic islets of two individuals with type 1 diabetes also recognized such hybrid peptides, suggesting that they may play an important role in driving disease.

    Science, this issue p. 711

  18. Biochemistry

    Spatial control of cellular enzymes

    1. Valda Vinson

    Purine is a building block of DNA and also a component of ATP that is used as an energy source in the cell. Enzymes involved in purine biosynthesis organize into dynamic bodies called purinosomes. French et al. found that purinosomes colocalize with mitochondria, organelles that generate ATP (see the Perspective by Ma and Jones). Dysregulation of mitochondria caused an increase in the number of purinosomes. This suggests a synergy, with the purinosomes supplying the purine required for ATP production and in turn using ATP in the biosynthetic pathway. A master regulator of cellular metabolism, mTOR, appears to mediate the association of purinosomes and mitochondria. This could make purine and ATP synthesis responsive to changes in the metabolic needs of the cell.

    Science, this issue p. 733; see also p. 670

  19. Evolution

    Finding the organelles' ancestors

    1. Julia Fahrenkamp-Uppenbrink

    In contrast to bacteria and archaea, eukaryotic cells contain organelles called mitochondria that generate chemical energy; plant cells also contain plastids, the sites of photosynthesis. In a Perspective, Ball et al. highlight recent research into how these organelles arose. The likely ancestors of mitochondria were pathogens that learned to survive within their archaeal host cells. Plastids have a more complex history that probably involved three partners: mitochondrion-containing unicellular eukaryotic host cell, a cyanobacterium, and a pathogen that helped the latter to survive in the host. Once these organelles became established, the scene was set for the evolution of multicellular life.

    Science, this issue p. 659

  20. Allergy

    Bringing atopic dermatitis up to scratch

    1. Angela Colmone

    Targeted therapies are transforming medicine, but complex diseases such as atopic dermatitis are difficult to target. Now, Jarrett et al. report a mechanism that links two contributors to atopic dermatitis pathogenesis: cutaneous inflammation and barrier dysfunction. They found that the dust mite allergen phospholipase (PLA2) induces neolipid antigens in human skin. These antigens can then be presented by the nonclassical MHC family member CD1a to CD1a-restricted T cells, which contribute to inflammation. The skin barrier protein filaggrin inhibits PLA2 and decreases inflammation. Indeed, individuals with filaggrin mutations experience severe atopic dermatitis. Thus barrier dysfunction and inflammation may be linked, and PLA2 may provide a target for treating atopic dermatitis.

    Sci. Transl. Med. 8, 325ra18 (2016).

  21. Plant Immunity

    Improving plant disease responses

    1. Pamela J. Hines

    Disease resistance in plants depends on genes that allow them to recognize when they are infected by a pathogen so that they can mount a timely defense response. Unfortunately, pathogens can often overcome endogenous disease resistance genes by evolving new virulence strategies that escape detection. Kim et al. modified the pathogen recognition systems in the model plant Arabidopsis thaliana to widen its reach. The approach should enable the development of crops with more durable disease resistance and hence reduce pesticide use and increase crop yields.

    Science, this issue p. 684