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[Research Article] Self-assembly of genetically encoded DNA-protein hybrid nanoscale shapes

Vie, 03/24/2017 - 00:00
We describe an approach to bottom-up fabrication that allows integration of the functional diversity of proteins into designed three-dimensional structural frameworks. A set of custom staple proteins based on transcription activator–like effector proteins folds a double-stranded DNA template into a user-defined shape. Each staple protein is designed to recognize and closely link two distinct double-helical DNA sequences at separate positions on the template. We present design rules for constructing megadalton-scale DNA-protein hybrid shapes; introduce various structural motifs, such as custom curvature, corners, and vertices; and describe principles for creating multilayer DNA-protein objects with enhanced rigidity. We demonstrate self-assembly of our hybrid nanostructures in one-pot mixtures that include the genetic information for the designed proteins, the template DNA, RNA polymerase, ribosomes, and cofactors for transcription and translation. Authors: Florian Praetorius, Hendrik Dietz

[Review] Vertically extensive and unstable magmatic systems: A unified view of igneous processes

Vie, 03/24/2017 - 00:00
Volcanoes are an expression of their underlying magmatic systems. Over the past three decades, the classical focus on upper crustal magma chambers has expanded to consider magmatic processes throughout the crust. A transcrustal perspective must balance slow (plate tectonic) rates of melt generation and segregation in the lower crust with new evidence for rapid melt accumulation in the upper crust before many volcanic eruptions. Reconciling these observations is engendering active debate about the physical state, spatial distribution, and longevity of melt in the crust. Here we review evidence for transcrustal magmatic systems and highlight physical processes that might affect the growth and stability of melt-rich layers, focusing particularly on conditions that cause them to destabilize, ascend, and accumulate in voluminous but ephemeral shallow magma chambers. Authors: Katharine V. Cashman, R. Stephen J. Sparks, Jonathan D. Blundy

[Research Article] Dynamics of cortical dendritic membrane potential and spikes in freely behaving rats

Vie, 03/24/2017 - 00:00
Neural activity in vivo is primarily measured using extracellular somatic spikes, which provide limited information about neural computation. Hence, it is necessary to record from neuronal dendrites, which can generate dendritic action potentials (DAPs) in vitro, which can profoundly influence neural computation and plasticity. We measured neocortical sub- and suprathreshold dendritic membrane potential (DMP) from putative distal-most dendrites using tetrodes in freely behaving rats over multiple days with a high degree of stability and submillisecond temporal resolution. DAP firing rates were several-fold larger than somatic rates. DAP rates were also modulated by subthreshold DMP fluctuations, which were far larger than DAP amplitude, indicating hybrid, analog-digital coding in the dendrites. Parietal DAP and DMP exhibited egocentric spatial maps comparable to pyramidal neurons. These results have important implications for neural coding and plasticity. Authors: Jason J. Moore, Pascal M. Ravassard, David Ho, Lavanya Acharya, Ashley L. Kees, Cliff Vuong, Mayank R. Mehta

[Research Article] Transition from turbulent to coherent flows in confined three-dimensional active fluids

Vie, 03/24/2017 - 00:00
Transport of fluid through a pipe is essential for the operation of macroscale machines and microfluidic devices. Conventional fluids only flow in response to external pressure. We demonstrate that an active isotropic fluid, composed of microtubules and molecular motors, autonomously flows through meter-long three-dimensional channels. We establish control over the magnitude, velocity profile, and direction of the self-organized flows and correlate these to the structure of the extensile microtubule bundles. The inherently three-dimensional transition from bulk-turbulent to confined-coherent flows occurs concomitantly with a transition in the bundle orientational order near the surface and is controlled by a scale-invariant criterion related to the channel profile. The nonequilibrium transition of confined isotropic active fluids can be used to engineer self-organized soft machines. Authors: Kun-Ta Wu, Jean Bernard Hishamunda, Daniel T. N. Chen, Stephen J. DeCamp, Ya-Wen Chang, Alberto Fernández-Nieves, Seth Fraden, Zvonimir Dogic

[Research Article] Cryo-EM structures of the triheteromeric NMDA receptor and its allosteric modulation

Vie, 03/24/2017 - 00:00
N-methyl-d-aspartate receptors (NMDARs) are heterotetrameric ion channels assembled as diheteromeric or triheteromeric complexes. Here, we report structures of the triheteromeric GluN1/GluN2A/GluN2B receptor in the absence or presence of the GluN2B-specific allosteric modulator Ro 25-6981 (Ro), determined by cryogenic electron microscopy (cryo-EM). In the absence of Ro, the GluN2A and GluN2B amino-terminal domains (ATDs) adopt “closed” and “open” clefts, respectively. Upon binding Ro, the GluN2B ATD clamshell transitions from an open to a closed conformation. Consistent with a predominance of the GluN2A subunit in ion channel gating, the GluN2A subunit interacts more extensively with GluN1 subunits throughout the receptor, in comparison with the GluN2B subunit. Differences in the conformation of the pseudo-2-fold–related GluN1 subunits further reflect receptor asymmetry. The triheteromeric NMDAR structures provide the first view of the most common NMDA receptor assembly and show how incorporation of two different GluN2 subunits modifies receptor symmetry and subunit interactions, allowing each subunit to uniquely influence receptor structure and function, thus increasing receptor complexity. Authors: Wei Lü, Juan Du, April Goehring, Eric Gouaux

[Editorial] UK science, post-Brexit

Vie, 03/24/2017 - 00:00
Nine months since the British vote to exit the European Union (“Brexit”), the UK science community's initial dismay has given way to hard-boiled determination to limit the damage it will do to universities and research. On 29 March, Prime Minister Theresa May is expected to give formal notification of the UK's intention to withdraw under Article 50 of the Lisbon Treaty, the constitutional basis of the EU. This will set in motion a 2-year period of intense negotiation on the terms of the UK's divorce, and any future agreements with the EU—with research just one line item on a long list of issues to be resolved. Author: James Wilsdon

[In Brief] News at a glance

Vie, 03/24/2017 - 00:00
In science news around the world, the San people of Southern Africa release a code of ethics to guide researchers wanting to study their culture or genes, a series of films documenting nuclear tests from the 1945 to 1962 is released on YouTube, U.K. regulators grant the first license for mitochondrial replacement therapy, a researcher is accused of putting his name to a paper partially ghost-written by employees at chemical giant Monsanto, and more. Also, the administration of U.S. President Donald Trump will reopen a review of a 2012 fuel efficiency agreement by automakers that would double efficiency by 2025. And the Trump administration also plans to rescind an Obama-era rule requiring public disclosure of the chemicals used in fracking on public lands.

[In Depth] Trump's 2018 budget proposal ‘devalues’ science

Vie, 03/24/2017 - 00:00
The 2018 budget proposal that President Donald Trump unveiled last week confirms two things that U.S. scientists have long suspected: The new president is no fan of research, and his administration has no overarching strategy for funding science. Deep proposed cuts to research at several agencies offer evidence that Trump doesn't see science—of any kind—as a spending priority. And along with neglect there's indifference. There's no telling how the National Science Foundation would fare, for example, because the budget blueprint doesn't mention it. In the meantime, scientists are also worried about the fate of this year's research budgets after Trump proposed cuts to the category that funds all civilian research. More angst: There's no word yet on whether the president will even appoint a science adviser, much less when he will fill dozens of senior slots at research agencies. Author: Jeffrey Mervis

[In Depth] Can flu shots help women get pregnant?

Vie, 03/24/2017 - 00:00
Two new clinical trials are testing whether flu vaccines increase the effectiveness of in vitro fertilization (IVF). The studies draw on new discoveries about the immune system's role in reproduction. Doctors used to think that the immune system had to shut down during pregnancy so that it wouldn't destroy the embryo. Now, researchers realize that the immune system remains active but learns to accept the embryo, developing what's known as tolerance. The trials will test whether flu shots increase tolerance toward the embryo and improve the success rate of IVF. One trial includes women undergoing IVF with embryos created from their own eggs, and the other trial includes women who receive embryos created from donor eggs.  Author: Mitch Leslie

[In Depth] Ma, where did they put T. rex?

Vie, 03/24/2017 - 00:00
A new study gives the long-standing dinosaur family tree an overhaul. Based on analyses of hundreds of traits gleaned from existing studies and fossils, the study strikes down a fundamental split of dinosaurs into "bird-hipped" and "reptile-hipped"; it also shifts the charismatic theropods—the group that includes Tyrannosaurus rex and eventually gave rise to birds—to a new spot on the tree, closer to the bird-hipped dinos. The reorganization of the tree suggests that hypercarnivory evolved in different groups through convergent evolution, and may upend the picture of where dinosaurs arose. But don't throw out your dog-eared dino books just yet, other researchers caution: This new family tree is likely to be debated for some time to come. Author: Carolyn Gramling

[In Depth] New Zealand temblor points to threat of compound quakes

Vie, 03/24/2017 - 00:00
A reassuring rule of thumb about earthquakes is breaking down. For decades, seismologists had assumed that individual faults—as well as isolated segments of longer faults—rupture independently of one another. That limits the maximum size of the potential earthquake that a fault zone can generate. But the magnitude-7.8 earthquake that struck New Zealand just after midnight on 14 November 2016—among the largest in the islands' modern history—has reduced that thinking to rubble. According to a new study, published online this week in Science, the heavy shaking in the Kaikoura quake was amassed by ruptures on at least 12 different faults, in some cases so far apart that they were thought to be immune to each other's influence. Author: Betsy Mason

[In Depth] In search for unseen matter, physicists turn to dark sector

Vie, 03/24/2017 - 00:00
Scientists hunting unseen dark matter are looking deeper into the shadows. With searches for a favored dark matter candidate—weakly interacting massive particles (WIMPs)—coming up empty, physicists are now turning to the hypothetical "dark sector": an entire shadow realm of hidden particles. This week, physicists will meet at the University of Maryland in College Park for a workshop, sponsored by the U.S. Department of Energy (DOE), to mull ideas for a possible $10 million short-term experiment that would complement the agency's current WIMP search and other dark-matter efforts. And many researchers believe DOE should focus on the dark sector. Whereas WIMPs would be a single massive particle tacked onto the standard model of known particles, the dark sector would consist of a slew of lighter particles and forces—such as a dark version of electromagnetism—with tenuous connections to known particles. To spot dark-sector particles, physicists will have to rethink their detection techniques, but the new experiment could be small and cheap, physicists say. Still, DOE officials warn that the $10 million isn't a sure thing. Author: Adrian Cho

[In Depth] Tweak makes U.S. nukes more precise—and deadlier

Vie, 03/24/2017 - 00:00
A small fix made in the name of "stockpile stewardship" is turning U.S. submarine–launched missiles into more precise weapons. An improved mechanism installed in aging warhead now makes it possible to adjust the height at which they detonate, according to three experts writing in The Bulletin of the Atomic Scientists. This vastly increases the weapons' efficiency, the experts say, creating the impression that submarine-launched weapons could be used in a first strike against Russia's fixed missile silos. About 500 such warheads have been deployed on submarines; more than 1000 updated warheads are in production. The innovation could create "a deeply destabilizing and dangerous strategic nuclear situation," the authors warn. Author: Eliot Marshall

[Feature] Fishy business

Vie, 03/24/2017 - 00:00
Two Swedish fish researchers, with the aid of five colleagues elsewhere in the world, have alleged fraud in a study on the effects of microplastics on larval fish published in Science by two scientists at Uppsala University (UU) in June 2016. The study supposedly took place at the Ar Research Station in Gotland, but the whistleblowers say it never happened, based on eyewitness testimony and other evidence. A preliminary investigation by UU dismissed the claims in August 2016; a second investigation, by an expert panel at Sweden's Central Ethical Review Board, is still ongoing. An expert hired by that panel filed a more damning report last February that raised the possibility of fraud. Now, both sides are awaiting the expert panel's final verdict, which may influence an ongoing debate about how Swedish institutions investigate research misconduct. Author: Martin Enserink

[Perspective] Macrophage, a long-distance middleman

Vie, 03/24/2017 - 00:00
Macrophages were first identified in transparent starfish larvae (Astropecten pentacanthus) more than a century ago, so it is fitting that a new function for macrophages would again be discovered in transparent marine larvae, this time from zebra fish (Danio rerio). On page 1317 of this issue, Eom and Parichy (1) reveal a wholly unexpected tissue-specific function of macrophages—their cardinal role in long-distance communication between nonimmune cells. In doing so, macrophages choreograph the patterning of pigment cells that eventually form the stripes on zebrafish. Author: Martin Guilliams

[Perspective] Powering up perovskite photoresponse

Vie, 03/24/2017 - 00:00
The most notable scientific milestone in photovoltaics in the past several years is the emergence of solar cells based on hybrid organic-inorganic perovskite materials. While conventional silicon and thin-film solar cells have seen steady improvements in their power-conversion efficiencies (PCEs) spanning several decades, hybrid perovskite solar cells have already reached a certified 22.1% PCE (1), matching conventional solar cell technologies in only a few years since their first device architecture was tested. Setting the stage for a disruptive technology in the field of photovoltaics is the seemingly winning combination of properties of hybrid perovskite materials: high absorption coefficient and a tunable energy band gap in wavelengths ideal for solar cells; long diffusion lengths and lifetimes for photogenerated charge carriers, which easily dissociate into efficiently collected electrons and holes; Earth-abundant elemental composition; and their compatibility with low-cost and low-temperature fabrication methods (2–5). On page 1288 of this issue, Blancon et al. (6) report on the observation of an enhanced photoresponse for layered perovskite materials. The results add, literally, a new dimension to the further development of high-performance perovskite solar cells. Authors: Osman M. Bakr, Omar F. Mohammed

[Perspective] Bringing proteins into the fold

Vie, 03/24/2017 - 00:00
Molecular engineers have become increasingly adept at repurposing life's building blocks to make custom self-assembled shapes. Because a single drop of solution contains billions of such shapes, DNA origami smiley faces (1), RNA stars (2), and designer protein polyhedra (3) may vastly outnumber most other human-made objects on Earth. These shapes lack immediate practical utility, but they transmit a powerful message: Researchers are beginning to understand how molecules self-assemble. On page 1283 of this issue, Praetorius and Dietz make another leap forward by demonstrating a novel class of nanostructures, namely DNA-protein hybrid shapes (4). This is an important advance because it provides a method to create human-designed shapes out of ingredients that are generally compatible with living systems. Author: Shawn M. Douglas

[Perspective] From chaos to order in active fluids

Vie, 03/24/2017 - 00:00
There are few sights more spectacular than the swarming of a school of fish or a flock of birds that suddenly gives way to a directional motion. Arguably, our admiration is rooted in the surprise that individual organisms, capable of self-propulsion on their own, organize to move en masse in a coherent fashion. Coherent motion is common in a large class of biological and synthetic materials that are often referred to as active matter. Such materials consist of particles immersed in a fluid that can extract energy from their surroundings (or internal fuel) and convert it into directed motion. Living organisms, biological tissues, rods on a vibrated plate, and self-phoretic colloids are just a few examples (1). Similar to schools of fish and flocks of birds, active matter often exhibits random swarming motion (2–5) that until now was impossible to control or use. On page 1284 of this issue, Wu et al. (6) demonstrate that an active fluid can be manipulated to flow in a particular direction without any external stimuli by confining it in microchannels. Author: Alexander Morozov

[Perspective] Using fire to promote biodiversity

Vie, 03/24/2017 - 00:00
Fire profoundly influences people, climate, and ecosystems (1). The impacts of this interaction are likely to grow, with climate models forecasting widespread increases in fire frequency and intensity because of rising global temperatures (2). However, the relationship between fire and biodiversity is complex (3, 4). Many plants and animals require fire for their survival, yet even in fire-prone ecosystems, some species and communities are highly sensitive to fire. Recent studies (2, 3, 5, 6) are helping to define fire regimes that support the conservation of species with different requirements in a rapidly changing world. Authors: L. T. Kelly, L. Brotons

[Perspective] Genes, environment, and “bad luck”

Vie, 03/24/2017 - 00:00
It is a human trait to search for explanations for catastrophic events and rule out mere “chance” or “bad luck.” When it comes to human cancer, the issue of natural causes versus bad luck was raised by Tomasetti and Vogelstein about 2 years ago (1). Their study, which was widely misinterpreted as saying that most cancers are due neither to genetic inheritance nor environmental factors but simply bad luck, sparked controversy. To date, a few hundred papers have been written in response, including (2–6), with some [e.g., (2)] coming to opposite conclusions. What is this controversy about? Tomasetti and Vogelstein concluded that 65% of the differences in the risk of certain cancers is linked to stem cell divisions in the various cancerous tissues examined (1). On page 1330 of this issue, Tomasetti et al. (7) provide further evidence that this is not specific to the United States. Authors: Martin A. Nowak, Bartlomiej Waclaw

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