Gravitational waves are expected to be radiated by supermassive black hole binaries formed during galaxy mergers. A stochastic superposition of gravitational waves from all such binary systems would modulate the arrival times of pulses from radio pulsars. Using observations of millisecond pulsars obtained with the Parkes radio telescope, we constrained the characteristic amplitude of this background, Ac,yr, to be <1.0 × 10−15 with 95% confidence. This limit excludes predicted ranges for Ac,yr from current models with 91 to 99.7% probability. We conclude that binary evolution is either stalled or dramatically accelerated by galactic-center environments and that higher-cadence and shorter-wavelength observations would be more sensitive to gravitational waves. Authors: R. M. Shannon, V. Ravi, L. T. Lentati, P. D. Lasky, G. Hobbs, M. Kerr, R. N. Manchester, W. A. Coles, Y. Levin, M. Bailes, N. D. R. Bhat, S. Burke-Spolaor, S. Dai, M. J. Keith, S. Osłowski, D. J. Reardon, W. van Straten, L. Toomey, J.-B. Wang, L. Wen, J. S. B. Wyithe, X.-J. Zhu

α-Chiral amines are key intermediates for the synthesis of a plethora of chemical compounds at industrial scale. We present a biocatalytic hydrogen-borrowing amination of primary and secondary alcohols that allows for the efficient and environmentally benign production of enantiopure amines. The method relies on a combination of two enzymes: an alcohol dehydrogenase (from Aromatoleum sp., Lactobacillus sp., or Bacillus sp.) operating in tandem with an amine dehydrogenase (engineered from Bacillus sp.) to aminate a structurally diverse range of aromatic and aliphatic alcohols, yielding up to 96% conversion and 99% enantiomeric excess. Primary alcohols were aminated with high conversion (up to 99%). This redox self-sufficient cascade possesses high atom efficiency, sourcing nitrogen from ammonium and generating water as the sole by-product. Authors: Francesco G. Mutti, Tanja Knaus, Nigel S. Scrutton, Michael Breuer, Nicholas J. Turner

Storage of photovoltaic and wind electricity in batteries could solve the mismatch problem between the intermittent supply of these renewable resources and variable demand. Flow batteries permit more economical long-duration discharge than solid-electrode batteries by using liquid electrolytes stored outside of the battery. We report an alkaline flow battery based on redox-active organic molecules that are composed entirely of Earth-abundant elements and are nontoxic, nonflammable, and safe for use in residential and commercial environments. The battery operates efficiently with high power density near room temperature. These results demonstrate the stability and performance of redox-active organic molecules in alkaline flow batteries, potentially enabling cost-effective stationary storage of renewable energy. Authors: Kaixiang Lin, Qing Chen, Michael R. Gerhardt, Liuchuan Tong, Sang Bok Kim, Louise Eisenach, Alvaro W. Valle, David Hardee, Roy G. Gordon, Michael J. Aziz, Michael P. Marshak

The efficiency and selectivity of hydrogen atom transfer from organic molecules are often difficult to control in the presence of multiple potential hydrogen atom donors and acceptors. Here, we describe the mechanistic evaluation of a mode of catalytic activation that accomplishes the highly selective photoredox α-alkylation/lactonization of alcohols with methyl acrylate via a hydrogen atom transfer mechanism. Our studies indicate a particular role of tetra-n-butylammonium phosphate in enhancing the selectivity for α C–H bonds in alcohols in the presence of allylic, benzylic, α-C=O, and α-ether C–H bonds. Authors: Jenna L. Jeffrey, Jack A. Terrett, David W. C. MacMillan

Antarctic ice-core data reveal that the atmosphere experienced abrupt centennial increases in CO2 concentration during the last deglaciation (~18 thousand to 11 thousand years ago). Establishing the role of ocean circulation in these changes requires high-resolution, accurately dated marine records. Here, we report radiocarbon data from uranium-thorium–dated deep-sea corals in the Equatorial Atlantic and Drake Passage over the past 25,000 years. Two major deglacial radiocarbon shifts occurred in phase with centennial atmospheric CO2 rises at 14.8 thousand and 11.7 thousand years ago. We interpret these radiocarbon-enriched signals to represent two short-lived (less than 500 years) “overshoot” events, with Atlantic meridional overturning stronger than that of the modern era. These results provide compelling evidence for a close coupling of ocean circulation and centennial climate events during the last deglaciation. Authors: Tianyu Chen, Laura F. Robinson, Andrea Burke, John Southon, Peter Spooner, Paul J. Morris, Hong Chin Ng

Ecological partnerships, or mutualisms, are globally widespread, sustaining agriculture and biodiversity. Mutualisms evolve through the matching of functional traits between partners, such as tongue length of pollinators and flower tube depth of plants. Long-tongued pollinators specialize on flowers with deep corolla tubes, whereas shorter-tongued pollinators generalize across tube lengths. Losses of functional guilds because of shifts in global climate may disrupt mutualisms and threaten partner species. We found that in two alpine bumble bee species, decreases in tongue length have evolved over 40 years. Co-occurring flowers have not become shallower, nor are small-flowered plants more prolific. We argue that declining floral resources because of warmer summers have favored generalist foraging, leading to a mismatch between shorter-tongued bees and the longer-tubed plants they once pollinated. Authors: Nicole E. Miller-Struttmann, Jennifer C. Geib, James D. Franklin, Peter G. Kevan, Ricardo M. Holdo, Diane Ebert-May, Austin M. Lynn, Jessica A. Kettenbach, Elizabeth Hedrick, Candace Galen

Mitochondria fulfill central functions in cellular energetics, metabolism, and signaling. The outer membrane translocator complex (the TOM complex) imports most mitochondrial proteins, but its architecture is unknown. Using a cross-linking approach, we mapped the active translocator down to single amino acid residues, revealing different transport paths for preproteins through the Tom40 channel. An N-terminal segment of Tom40 passes from the cytosol through the channel to recruit chaperones from the intermembrane space that guide the transfer of hydrophobic preproteins. The translocator contains three Tom40 β-barrel channels sandwiched between a central α-helical Tom22 receptor cluster and external regulatory Tom proteins. The preprotein-translocating trimeric complex exchanges with a dimeric isoform to assemble new TOM complexes. Dynamic coupling of α-helical receptors, β-barrel channels, and chaperones generates a versatile machinery that transports about 1000 different proteins. Authors: Takuya Shiota, Kenichiro Imai, Jian Qiu, Victoria L. Hewitt, Khershing Tan, Hsin-Hui Shen, Noriyuki Sakiyama, Yoshinori Fukasawa, Sikander Hayat, Megumi Kamiya, Arne Elofsson, Kentaro Tomii, Paul Horton, Nils Wiedemann, Nikolaus Pfanner, Trevor Lithgow, Toshiya Endo

Long terminal repeat (LTR) retrotransposons are an abundant class of genomic parasites that replicate by insertion of new copies into the host genome. Fungal LTR retrotransposons prevent mutagenic insertions through diverse targeting mechanisms that avoid coding sequences, but conserved principles guiding their target site selection have not been established. Here, we show that insertion of the fission yeast LTR retrotransposon Tf1 is guided by the DNA binding protein Sap1 and that the efficiency and location of the targeting depend on the activity of Sap1 as a replication fork barrier. We propose that Sap1 and the fork arrest it causes guide insertion of Tf1 by tethering the integration complex to target sites. Authors: Jake Z. Jacobs, Jesus D. Rosado-Lugo, Susanne Cranz-Mileva, Keith M. Ciccaglione, Vincent Tournier, Mikel Zaratiegui

This issue of Science includes the program of the 2016 AAAS Annual Meeting. 2016 “Session I” Meetings will be held between January 9 and March 25 in Ventura, CA and Galveston, TX in the United States, and internationally in the Tuscany region of Italy. A PDF of the program as it appears in this issue is available here; for more information on the meeting (including registration forms and information on accommodations), please visit www.grc.org.

Engineered systems of genes and other molecular components created through synthetic biology make medical treatments more effective and promise cures for a range of health problems. Perhaps equally important, recent technologies make it easier for a broader range of scientists to apply synthetic-biology approaches that drive expanding clinical applications, from designing new diagnostics and building molecularly engineered tissues to developing new drugs and vaccines.Read the Feature (Full-Text HTML)Read the Feature (PDF)Read New Products (PDF) Author: Mike May

A weekly roundup of information on newly offered instrumentation, apparatus, and laboratory materials of potential interest to researchers.

On this week's show: 3-parent gene therapy to treat mitochondrial diseases and a roundup of daily news stories.

Authors: Francisco J. Quintana, Kristjan Pltzer

Author: Rachel Yoho

Abstract

Phosphorylase kinase (PhK) is a hexadecameric (αβγδ)4 enzyme complex that upon activation by phosphorylation stimulates glycogenolysis. Due to its large size (1.3 MDa), elucidating the structural changes associated with the activation of PhK has been challenging, although phosphoactivation has been linked with an increased tendency of the enzyme's regulatory β-subunits to self-associate. Here we report the effect of a peptide mimetic of the phosphoryltable N-termini of β on the selective, zero-length, oxidative crosslinking of these regulatory subunits to form β–β dimers in the nonactivated PhK complex. This peptide stimulated β–β dimer formation when not phosphorylated, but was considerably less effective in its phosphorylated form. Because this peptide mimetic of β competes with its counterpart region in the nonactivated enzyme complex in binding to the catalytic γ-subunit, we were able to formulate a structural model for the phosphoactivation of PhK. In this model, the nonactivated state of PhK is maintained by the interaction between the nonphosphorylated N-termini of β and the regulatory C-terminal domains of the γ-subunits; phosphorylation of β weakens this interaction, leading to activation of the γ-subunits.

Abstract

The expression of recombinant [FeFe]-hydrogenases is an important step for the production of large amount of these enzymes for their exploitation in biotechnology and for the characterization of the protein-metal cofactor interactions. The correct assembly of the organometallic catalytic site, named H-cluster, requires a dedicated set of maturases that must be coexpressed in the microbial hosts or used for in vitro assembly of the active enzymes. In this work, the effect of the post-induction temperature on the recombinant expression of CaHydA [FeFe]-hydrogenase in E. coli is investigated. The results show a peculiar behavior: the enzyme expression is maximum at lower temperatures (20°C), while the specific activity of the purified CaHydA is higher at higher temperature (30°C), as a consequence of improved protein folding and active site incorporation.

by Alice Carolyn McHardy

by Florian Markowetz

by Pete Riley, Michal Ben-Nun, Jon A. Linker, Angelia A. Cost, Jose L. Sanchez, Dylan George, David P. Bacon, Steven Riley

The potential rapid availability of large-scale clinical episode data during the next influenza pandemic suggests an opportunity for increasing the speed with which novel respiratory pathogens can be characterized. Key intervention decisions will be determined by both the transmissibility of the novel strain (measured by the basic reproductive number R0) and its individual-level severity. The 2009 pandemic illustrated that estimating individual-level severity, as described by the proportion pC of infections that result in clinical cases, can remain uncertain for a prolonged period of time. Here, we use 50 distinct US military populations during 2009 as a retrospective cohort to test the hypothesis that real-time encounter data combined with disease dynamic models can be used to bridge this uncertainty gap. Effectively, we estimated the total number of infections in multiple early-affected communities using the model and divided that number by the known number of clinical cases. Joint estimates of severity and transmissibility clustered within a relatively small region of parameter space, with 40 of the 50 populations bounded by: pC, 0.0133–0.150 and R0, 1.09–2.16. These fits were obtained despite widely varying incidence profiles: some with spring waves, some with fall waves and some with both. To illustrate the benefit of specific pairing of rapidly available data and infectious disease models, we simulated a future moderate pandemic strain with pC approximately ×10 that of 2009; the results demonstrating that even before the peak had passed in the first affected population, R0 and pC could be well estimated. This study provides a clear reference in this two-dimensional space against which future novel respiratory pathogens can be rapidly assessed and compared with previous pandemics.

Journal of the American Chemical SocietyDOI: 10.1021/jacs.5b08313