This Week in Science

Science  24 Jun 2016:
Vol. 352, Issue 6293, pp. 1530
  1. Neurodevelopment

    Versatile embryonic neural crest cells

    1. Pamela J. Hines

    Malleable neural crest cells help chick embryos develop

    PHOTO: JEROME WEXLER / SCIENCE SOURCE

    Neural crest cells wander far and wide through the developing vertebrate embryo to build tissues such as the jaw and peripheral nerves. Simoes-Costa et al. show, studying chick embryos, that not all neural crest cells are alike. The expression of a handful of transcription factors identifies cranial neural crest cells as distinct from trunk neural crest cells. Ectopic expression of some of these factors caused trunk neural crest cells to function as cranial neural crest cells. Thus, embryonic neural crest cells carry subspecialties that are defined but malleable.

    Science, this issue p. 1570

  2. Biochemistry

    Making error-free DNA from RNA

    1. Guy Riddihough

    DNA polymerase enzymes copy DNA into new strands of identical DNA. Reverse transcriptase (RT) enzymes copy RNA into DNA. Unlike many DNA polymerases, RT enzymes do not have a proofreading function that checks for errors in the newly synthesized DNA. Ellefson et al. use in vitro directed evolution and protein engineering to build an error-correcting RT from a prokaryotic DNA polymerase. The RT “xenopolymerase” shows increased fidelity as compared to natural RTs and should streamline and increase the precision of transcriptomics methods.

    Science, this issue p. 1590

  3. Quantum Information

    How to single out the right atoms

    1. Jelena Stajic

    For a quantum computer to be useful, its qubits have to be able to change their state in response to external stimuli. But when a large number of qubits are packed in a three-dimensional (3D) structure to optimize the use of space, altering one qubit can unintentionally change the state of others. Wang et al. devised a clever way to perform high-fidelity quantum gates only on intended qubits in a 3D array of Cs atoms. Although the operation initially changed the state of some of the other atoms, additional manipulation recovered their original state. The technique may be applicable to other quantum computing implementations.

    Science, this issue p. 1562

  4. Innate Immunity

    Mounting the intestinal barricades

    1. Caroline Ash

    Gut microbiota are important for health and well-being, but they need to be kept under control and prevented from doing any harm. Birchenough et al. investigated the microbial molecules that trigger protective mucus secretion from a class of goblet cells in the colon. Once the molecules are detected, an alarm signal is transmitted from these cells via innate immune signal mediators and inflammasome components to adjacent cells, generating more mucus and repelling the invaders. Subsequently, the sentinel goblet cells are expelled from the epithelium and their remains may also add to the protective barricade.

    Science, this issue p. 1535

  5. Structural Biology

    Holding kinases at the ready

    1. Valda Vinson

    About 60% of kinases only reach their active state in the presence of the molecular chaperone Hsp90 and its co-chaperone Cdc37. It is unclear how the chaperones facilitate kinase function or why only some kinases are chaperone-dependent. Verba et al. determined a 3.9 Å cryo–electron microscopy structure of Hsp90:Cdc37 in complex with the kinase Cdk4. Together, Hsp90 and Cdc37 trap the kinase in an open, partially unfolded state. Taking on this state probably has direct functional benefits.

    Science, this issue p. 1542

  6. Organic Chemistry

    Catalysis gets all tied up in knots

    1. Jake Yeston

    Over the past decade, chemists have used metal ion templating to prepare a wide variety of knotted molecular strands. Marcos et al. now show that one such pentafoil knot can be applied to catalysis. When held taut by zinc ions, the knot can capture a chloride or bromide ion from a halocarbon, thereby unleashing the reactivity of the residual cation for applications such as Lewis acid catalysis. Removing the zinc ions lowers the knot's affinity for the halides, offering a reversible modulation mechanism for the catalysis.

    Science, this issue p. 1555

  7. Nanomaterials

    Multimetal nanoparticle synthesis

    1. Phil Szuromi

    Multicomponent nanoparticles can be difficult to synthesize. Rather than mixing in one type of particle, the compounds often separate and form distinct particles. Using dip-pen lithography, Chen et al. show how adding reactants to very small volumes forces the reactants to form single particles containing various combinations of five different transition metal ions. Scanning transmission electron microscopy and energy-dispersive x-ray spectroscopy revealed the shapes of the nanoparticles and how metallic composition varied within them. For example, the quinary particle containing gold, silver, cobalt, copper, and nickel consisted of three domains of binary alloys.

    Single nanoparticles can contain multiple domains of transition metal ion alloys.

    PHOTO: CHEN ET AL.

    Science, this issue p. 1565

  8. Cystic Fibrosis

    Mini-guts for testing drug therapy

    1. Orla M. Smith

    Cystic fibrosis is caused by mutations in the CFTR gene, which reduce the function of the CFTR protein. New drugs for treating cystic fibrosis modulate CFTR protein function, but drug efficacy is dependent on which CFTR mutation a patient carries. Dekkers et al. show that the efficacy of these drugs can be individually assessed using epithelial cells cultured as mini-guts from rectal biopsies from cystic fibrosis patients. The drug response observed in these rectal organoids can help predict which patients may be potential responders to the drug. This preclinical test may help to quickly identify responders to CFTR-modulating drug therapy, even when patients carry very rare CFTR mutations.

    Sci. Transl. Med. 8, 344ra84 (2016).

  9. Immunology

    Nanoparticles restore tolerance

    1. John F. Foley

    Autoimmune diseases, such as type 1 diabetes, are caused by immune cells attacking healthy cells. One way to treat type 1 diabetes is to activate T regulatory (Treg) cells to suppress inflammatory T cell activity and restore tolerance, so that the inflammatory T cells stop destroying pancreatic β cells. Yeste et al. used gold nanoparticles to induce tolerance in a mouse model of type 1 diabetes. The mice had more Treg cells and less severe disease symptoms when given nanoparticles coated with proteins that induced tolerance. Nanoparticle-based therapies may be useful in restoring tolerance in other autoimmune diseases as well.

    Sci. Signal. 9, ra61 (2016).

  10. Distant Galaxies

    Shining brightly in the early universe

    1. Keith T. Smith

    Galaxies that formed early in the history of the universe were powerful sources of ultraviolet radiation. This radiation ionized the surrounding intergalactic medium during the “epoch of reionization.” Inoue et al. detected atomic emission lines from a galaxy at high redshift—seen as it was when the universe was only ~5% of its current age (see the Perspective by De Breuck). Data from optical, infrared, and submillimeter observatories determined its gas and dust content and the amount of ultraviolet radiation it emitted. Studying similar galaxies in such a manner will allow astronomers to determine how the first galaxies formed, evolved, and influenced their surroundings.

    Science, this issue p. 1559; see also p. 1520

  11. Microbiota

    Gut microbiota and undernutrition

    1. Caroline Ash

    Poor nutrition during the early years of life can have severe consequences for subsequent skeletal, immunological, and intellectual development. Blanton et al. review the evidence showing that undernutrition is not caused by food insecurity alone. Other factors range from the length of the breastfeeding period and the availability of milk oligosaccharides, enteropathogen exposure, and enteric dysfunction marked by villus atrophy and loss of gut barrier function. Unfortunately, the current practice of nutritional restoration with or without antibiotic treatment may not be effective in the longer term. Differences in the succession of microbial establishment and maturity might contribute to family discordances in nutritional status. Thus, microbiota-directed therapeutics could be a promising route to nutritional restoration in these children.

    Science, this issue p. 1533

  12. DNA Nanotechnology

    Simplifying DNA origami design

    1. Phil Szuromi

    Many intricate nanostructures have been made with DNA origami. This process occurs when a long DNA scaffold develops a particular shape after hybridization with short staple strands. Most designs, however, require a difficult iterative procedure of refining the base pairing. Veneziano et al. now report algorithms that automate the design of arbitrary DNA wireframe structures. Synthesizing and structurally characterizing a variety of nanostructures allowed for verification of the algorithms' accuracy.

    Science, this issue p. 1534

  13. Quantum Physics

    Quantum enhanced metrology

    1. Ian S. Osborne

    Exploiting the quantum-mechanical properties of quantum systems offer the possibility of developing devices for enhanced precision measurement and sensing applications. These devices have, however, required low-noise detection capabilities that have hampered their development. Hosten et al. describe a method that manipulates a coherent cloud of cold rubidium atoms in a way that relaxes the ultrasensitive detection requirements. The general method may be applied to other coherent quantum systems.

    Science, this issue p. 1552

  14. Climate Change

    Coming to a drought near you

    1. Julia Fahrenkamp-Uppenbrink

    Extreme weather events such as droughts and storms are rarely out of the headlines. Is climate change influencing their occurrence and severity? As Stott explains in a Perspective, researchers are now able to determine the contribution of climate change to individual extreme temperature events; for example, the extremely hot conditions in east China in 2013 have become 60 times more likely as a result of climate change. However, determining the contribution of climate change to extreme precipitation events remains difficult, in part because models capture rainfall extremes less accurately than they do temperature extremes.

    Science, this issue p. 1517

  15. Ocean Biology

    The microbial key to coral reef health

    1. Julia Fahrenkamp-Uppenbrink

    Coral reefs around the world are under threat from global warming, overfishing, and pollution. Ocean warming is particularly dangerous, causing bleaching that can lead to the death of the coral. In a Perspective, Ainsworth and Gates explains that the microbes associated with coral reefs are critical to reef survival. Corals that have more pathogenic bacteria are more likely to die after bleaching. The loss of beneficial bacteria has also been linked to the development of lesions and tissue necrosis in corals. If climate change leads to reefs with lower coral diversity, reduced microbial diversity is likely to result, making the reefs less resilient to further stress.

    Science, this issue p. 1518

  16. Organic Devices

    Mind the mobilities

    1. Phil Szuromi

    The operational speed of devices such as transistors depends on how fast charge carriers move through their active semiconductor material. In a Perspective, McCulloch et al. discuss how several recent claims of very high carrier mobilities in organic semiconductors overstate the values by at least an order of magnitude. These indirect measurements based on the transistor devices themselves can be flawed because the modeling of the current flow is inadequate.

    Science, this issue p. 1521

  17. Prostate Development

    Clues to cancer from an identity change

    1. Paula A. Kiberstis

    The prostate and seminal vesicle have closely related developmental histories and both are regulated by the same androgenic hormones. A better understanding of the molecular mechanisms controlling the development of the two tissues could help solve why cancer arises frequently in the prostate but only rarely in seminal vesicles. Working with cell and mouse models, Dutta et al. show that forced expression of a single gene, the homeobox gene NKX3.1, causes seminal vesicle epithelium to differentiate into prostate. NKX3.1 regulates the expression of a gene program associated with prostate differentiation by interacting with the G9a histone methyltransferase. Disruption of this regulatory network probably contributes to prostate cancer development.

    Science, this issue p. 1576

  18. Driving Ethics

    Codes of conduct in autonomous vehicles

    1. Barbara R. Jasny

    When it becomes possible to program decision-making based on moral principles into machines, will self-interest or the public good predominate? In a series of surveys, Bonnefon et al. found that even though participants approve of autonomous vehicles that might sacrifice passengers to save others, respondents would prefer not to ride in such vehicles (see the Perspective by Greene). Respondents would also not approve regulations mandating self-sacrifice, and such regulations would make them less willing to buy an autonomous vehicle.

    Science, this issue p. 1573; see also p. 1514

  19. Quantum Simulation

    Bosons refusing to thermalize in 2D

    1. Jelena Stajic

    Messy, interacting quantum-mechanical systems are difficult to analyze theoretically. In a single spatial dimension, the calculations are still tractable, and experiments have recently confirmed the prediction that sufficiently strong disorder can disrupt the transport of interacting particles. In two dimensions, however, the theoretical blueprint is missing. Choi et al. used single-site imaging of cold 87Rb atoms in an optical lattice to show that similar localization occurs in two-dimensional (2D) systems. The study highlights the power of quantum simulation to solve problems that are currently inaccessible to classical computing techniques.

    Science, this issue p. 1547

  20. Mucosal Immunology

    Location matters for immunosuppression

    1. Kristen L. Mueller

    In the gut, food antigens and resident microbes can trigger unwanted immune responses. Immunosuppressive cell types in the gut, such as regulatory T cells (Tregs) and intraepithelial T lymphocytes (IELs), help to keep these responses at bay. Sujino et al. report that the specific anatomical location within the gut shapes the properties of the suppressive T cell populations that reside there (see the Perspective by Colonna and Cervantes-Barragan). Using mice, they find that Tregs primarily reside in the lamina propria. Tregs migrate to the intestinal epithelium, where they convert to IELs in a process that depends on the microbiota and the loss of a specific transcription factor. Tregs and IELs also play distinct but complementary roles in suppressing intestinal inflammation.

    Science, this issue p. 1581; see also p. 1515

  21. Polymers

    Highly branched polymers deliver

    1. Philip Yeagle

    Tantalizing promise, largely unfulfilled, haunts gene therapy for human disease. Among several barriers to success, efficient gene delivery to targeted cells remains daunting. Zhou et al. broke one barrier through the synthesis of a new class of delivery vector. The pathway results in the synthesis of highly branched poly(β-amino ester) (HPAE), using a one-pot Michael addition. The transfection efficiency of HPAE over existing vectors improved by as much as three orders of magnitude. Gene delivery by HPAE was able to correct a genetic defect in a recessive dystrophic epidermolysis bullosa graft mouse model.

    Sci. Adv. 10.1126.sciadv.1600102 (2016).

  22. Neurogenomics

    Single-nucleus gene expression

    1. Laura M. Zahn

    Identifying the genes expressed at the level of a single cell nucleus can better help us understand the human brain. Lake et al. developed a single-nuclei sequencing technique, which they applied to cells in classically defined Brodmann areas from a postmortem brain. Clustering of gene expression showed concordance with the area of origin and defining 16 neuronal subtypes. Both excitatory and inhibitory neuronal subtypes show regional variations that define distinct cortical areas and exhibit how gene expression clusters may distinguish between distinct cortical areas. This method opens the door to widespread sampling of the genes expressed in a diseased brain and other tissues of interest.

    Science, this issue p. 1586