This Week in Science

Science  13 Jan 2017:
Vol. 355, Issue 6321, pp. 143
  1. Brain Research

    Are you aware how well you remember?

    1. Peter Stern

    Research in macaques reveals the seat of metamemory.

    CREDITS (TOP TO BOTTOM): JEAN-FRANCOIS LEMONNIER/UNIVERSITY OF MANCHESTER; ALAIN ROLLI/GETTY IMAGES

    Self-monitoring and evaluation of our own memory is a mental process called metamemory. For metamemory, we need access to information about the strength of our own memory traces. The brain structures and neural mechanisms involved in metamemory are completely unknown. Miyamoto et al. devised a test paradigm for metamemory in macaques, in which the monkeys judged their own confidence in remembering past experiences. The authors combined this approach with functional brain imaging to reveal the neural substrates of metamemory for retrospection. A specific region in the prefrontal brain was essential for meta mnemonic decision-making. Inactivation of this region caused selective impairment of metamemory, but not of memory itself.

    Science, this issue p. 188

  2. Protein Design

    Designing proteins with cavities

    1. Valda Vinson

    In de novo protein design, creating custom-tailored binding sites is a particular challenge because these sites often involve nonideal backbone structures. For example, curved b sheets are a common ligand binding motif. Marcos et al. investigated the principles that drive β-sheet curvature by studying the geometry of β sheets in natural proteins and folding simulations. In a step toward custom design of enzyme catalysts, they used these principles to control β-sheet geometry and design proteins with differently shaped cavities.

    Science, this issue p. 201

  3. Cancer

    Initiating an antitumor attack

    1. Yevgeniya Nusinovich

    Cancer is notorious for relapsing after treatment. Such relapses are driven by tumor-initiating cells, a type of stem cell that gives rise to tumors. Damelin et al. determined that a protein called PTK7 is frequently present on tumor-initiating cells and developed an antibody-drug conjugate targeting it. In mouse models of several tumor types, the therapy reduced tumor-initiating cells and outperformed standard chemotherapy. The antibody-drug conjugate also reduced tumor angiogenesis and promoted antitumor immunity, possibly contributing to its effectiveness.

    Sci. Transl. Med. 9, eaag2611 (2017).

  4. Structural Biology

    Poised for the second step of splicing

    1. Valda Vinson

    In eukaryotes, noncoding sequences in transcribed precursor mRNA are cut out by a dynamic macromolecular machine, the spliceosome. This involves two sequential reactions. The first cuts one end of the noncoding intron and loops it back on itself to form an intron lariat, and the next excises the intron and ligates the coding mRNA. Insights into the first step of splicing have come from the structures of two intermediates: the Bact complex, which is primed for catalysis, and the C complex, which is formed after the first splicing reaction. Yan et al. now report a high-resolution structure of the step II catalytically activated spliceosome (the C* complex). This structure shows conformational changes that position catalytic motifs to accomplish the second splicing reaction.

    Science, this issue p. 149

  5. Quantum Electronics

    Inducing strong coupling

    1. Ian S. Osborne

    Quantum dots, or artificial atoms, are being pursued as prospective building blocks for quantum information processing architectures. Communication with other, distant quantum dots requires strong coupling between photons and the electronic states of the dots. Mi et al. used double quantum dots defined in silicon and embedded in a superconducting cavity to achieve such coupling. This demonstration in an industry-relevant material bodes well for the large-scale development of semiconductor-based quantum processors.

    Science, this issue p. 156

  6. Cell Biology

    Phages build themselves a wall

    1. Stella M. Hurtley

    A nucleus-like compartment in phage-infected bacteria

    CREDIT: CHAIKEERATISAK ET AL.

    The compartmentalization of DNA replication away from other cytoplasmic events is a key feature of the cell nucleus. Chaikeeratisak et al. studied the replication of the very large Pseudomonas bacteriophage 201φ2-1 by using fluorescence microscopy and cryo–electron tomography. They found that the phage assembled a nucleus-like compartment when it infected a bacterial cell. The phage genome was completely enclosed by an apparently contiguous protein shell, within which DNA replication, recombination, and transcription occurred. Translation, precursor biosynthesis, and viral assembly occurred outside the structure.

    Science, this issue p. 194

  7. Bacterial Prions

    Prions enter another domain of life

    1. Stella M. Hurtley

    Prions are self-propagating protein aggregates, discovered in connection with the fatal transmissible spongiform encephalopathies in mammals. Prions have also been identified in fungi, where they act as protein-based elements of inheritance. Although prions have been uncovered in evolutionarily diverse eukaryotic species, it is not known whether prions exist in bacteria. Yuan and Hochschild report the identification of a bacterial protein—the transcription termination factor Rho from Clostridium botulinum—that exhibits the defining hallmarks of a prion-forming protein.

    Science, this issue p. 198

  8. Neuroscience

    Channeling pain through GPCRs

    1. Nancy R. Gough

    Mutations in Nav1.7 result in the absence of sensitivity to pain, but drugs targeting this sodium channel are not effective as pain relievers. Isensee et al. found that the absence of Nav1.7 altered the signaling efficiency of G protein–coupled receptors (GPCRs) in pain-sensing neurons of the spinal cord. Normally, pain-promoting serotonin receptor signaling is balanced by pain-relieving mu opioid receptor signaling. In mice lacking Nav1.7, the balance was shifted so that the opioid arm dominated, resulting in neurons that were less active and more responsive to pain-relieving signals.

    Sci. Signal. 10, eaah4874 (2017).

  9. Electrochemistry

    Better living through water-splitting

    1. Jake Yeston

    Chemists have known how to use electricity to split water into hydrogen and oxygen for more than 200 years. Nonetheless, because the electrochemical route is inefficient, most of the hydrogen made nowadays comes from natural gas. Seh et al. review recent progress in electrocatalyst development to accelerate water-splitting, the reverse reactions that underlie fuel cells, and related oxygen, nitrogen, and carbon dioxide reductions. A unified theoretical framework highlights the need for catalyst design strategies that selectively stabilize distinct reaction intermediates relative to each other.

    Science, this issue p. 10.1126/science.aad4998

  10. Ribosome Assembly

    A machine for building ribosomes

    1. Guy Riddihough

    The ribosome is a very large protein and RNA complex responsible for the difficult process of synthesizing proteins. Construction of the ribosome itself involves several molecular machines and an army of helper proteins and RNAs. Chaker-Margot et al. determined the structure of one of those machines, the yeast small subunit processome. The structure reveals how the processome helps in the maturation of individual domains of the ribosome and suggests that the mechanism involves a molecular motor to drive conformational changes.

    Science, this issue p. 10.1126/science.aal1880

  11. Superconductivity

    Squeezing out the oddness

    1. Jelena Stajic

    The material Sr2RuO4 has long been thought to exhibit an exotic, odd-parity kind of superconductivity, not unlike the superfluidity in 3He. How would perturbing this material's electronic structure affect its superconductivity? Steppke et al. put the material under large uniaxial pressure and found that the critical temperature more than doubled and then fell as a function of strain (see the Perspective by Shen). The maximum critical temperature roughly coincided with the point at which the material's Fermi surface underwent a topological change. One intriguing possibility is that squeezing changed the parity of the superconducting gap from odd to even.

    Science, this issue p. 10.1126/science.aaf9398; see also p. 133

  12. Organic Chemistry

    A cyclic catalyst to pair up sugars

    1. Jake Yeston

    Linking sugar molecules together to make complex carbohydrates is a geometrical challenge. For a six-carbon sugar such as glucose, there are six different possible linkage sites and also two possible configurations in which to anchor the incipient bond. Park et al. developed a ring-shaped, dimeric catalyst that pairs sugars after one of them has been modified with a chloride. The thiourea-based catalyst appears to pull away the chloride while simultaneously activating the incoming second sugar. The resultant bond-forming process reliably inverts the initial C–Cl configuration.

    Science, this issue p. 162

  13. Materials Science

    Pin the tail on the hydrogens

    1. Marc S. Lavine

    X-ray diffraction has been the method of choice for determining the positions of atoms within a crystal. However, the technique works better for atoms with higher atomic numbers and requires single crystals of a minimum size. Palatinus et al. used electron diffraction, a technique of increasing importance for analyzing very small crystals, to identify the positions of hydrogen atoms in organic and inorganic materials (see the Perspective by McCusker).

    Science, this issue p. 166; see also p. 136

  14. Structural Biology

    Redox metabolite role in biofilms

    1. Caroline Ash

    In the microbial world, the chemical diversity of secreted metabolites is vast, and their physiological roles are underexplored. Costa et al. studied the redox-active secondary metabolite pyocyanin, which is produced by the opportunistic pathogen Pseudomonas aeruginosa. Pyocyanin mediates the generation of thick biofilms containing extracellular DNA that are important in pathogenesis. The authors characterized the demethylase PodA, which catalyzes the conversion of pyocyanin to hydroxyphenazine and deranges biofilm formation. PodA could represent a therapeutic lead for intractable bacterial infections.

    Science, this issue p. 170

  15. Plant Ecology

    Soil biota and plant diversity

    1. Andrew M. Sugden

    Soil biota, including symbionts such as mycorrhizal fungi and nitrogen-fixing bacteria, as well as fungal and bacterial pathogens, affect terrestrial plant diversity and growth patterns (see the Perspective by van der Putten). Teste et al. monitored growth and survival in Australian shrubland plant species paired with soil biota from plants of the same species and from other plants that use different nutrient acquisition strategies. Plant-soil feedbacks appear to drive local plant diversity through interactions between the different types of plants and their associated soil biota. Bennett et al. studied plant-soil feedbacks in soil and seeds from 550 populations of 55 species of North American trees. Feedbacks ranged from positive to negative, depending on the type of mycorrhizal association, and were related to how densely the same species occurred in natural populations.

    Science, this issue p. 134, p. 173; see also p. 181

  16. Brain Research

    How to get to place B

    1. Peter Stern

    We constantly navigate around our environment. This means moving from our current location, place A, to a new goal, place B. We have recently learned much about spatial maps in the brain in which place cells indicate current location. However, it is unclear how navigational goals are represented in the brain. Sarel et al. describe a group of neurons in the brains of bats that are tuned to goal direction and distance relative to the bat's current position as it flies toward its goal. The finding elucidates the computations involved in spatial navigation.

    Science, this issue p. 176

  17. Memory Processing

    Parallel computation in memory-making

    1. Peter Stern

    The hippocampus plays a central role in the encoding, consolidation, and recall of memories. Consolidation and recall are thought to be executed by the replay of previously acquired memory traces by hippocampal cell assemblies. The hippocampus is thus considered to be the initiator of memory redistribution processes. However, O'Neill et al. now report that the superficial layers of the medial entorhinal cortex show replay events that are independent of hippocampal activity (see the Perspective by Moser and Gardner). Computations in memory systems may thus be organized in a less hierarchical, more parallel way than previously thought.

    Science, this issue p. 184; see also p. 131

  18. Climate Change

    Faster tree growth is no panacea

    1. Julia Fahrenkamp-Uppenbrink

    Climate warming, nitrogen deposition, and (in fertile ecosystems) elevated carbon dioxide may cause plants to grow faster. Can this growth stimulation lead to higher carbon storage in existing forests and help to mitigate climate change? In a Perspective, Körner argues that the carbon capital of a forest is set by the residence time of carbon in organic matter, not by the rate of tree growth. Faster growth commonly shortens the life span of trees and so does not help to store more carbon in the long term.

    Science, this issue p. 130

  19. Neurophysiology

    More light on dopamine receptors

    1. Philip Yeagle

    The dopamine D4 receptor is a G protein–coupled receptor that has been linked to attention deficit hyperactivity disorder and substance use disorders. Bonaventura et al. found that mutations in a key portion of this receptor had functional consequences. The receptor consists of seven transmembrane helices (TMs) connected by loops. The third intracellular loop between TM6 and TM7 is longer in the polymorphic variant D4.7R. Expression of this loop in the D4 receptor reduced release of corticostriatal glutamate. The findings provide insight into the role of D4 receptor variations in some neuropsychiatric syndromes and the effects of certain psychostimulants.

    Sci. Adv. 10.1126.sciadv.1601631 (2017).

  20. Immunotherapy

    TAMpering with tumors

    1. Angela Colmone

    Immunotherapeutic antibodies are a promising cancer therapy, but little is known about the nontargeted effects of these antibodies on immune cells through Fc receptor binding. Tumor-associated macrophages (TAMs) and neutrophils (TANs), which have been implicated in both promoting and inhibiting tumor growth, express abundant Fcγ receptors. Lehmann et al. examined these cells in tumors growing in different sites (skin and lung). The organ environment determined which TAM and TAN subpopulations contributed to antibody-dependent tumor immunotherapy. These data may help fine-tune therapeutic strategies to target only cells that promote tumors.

    Sci. Immunol. 2, eaah6413 (2017).

  21. Molecular Knots

    Three strands ironed closely together

    1. Jake Yeston

    It is not uncommon when braiding hair or bread to intertwine three different strands. At the molecular level, however, synthetic knots have thus far been restricted to architectures accessible from two-strand braids. Danon et al. used iron ion coordination to guide three organic ligand strands to form a knot geometry with eight separate crossings.

    Science, this issue p. 159