Chatters et al. (Reports, 16 May 2014, p. 750) reported the retrieval of DNA sequences from a 12,000- to 13,000-year-old human tooth discovered in an underwater cave in Mexico’s Yucatan peninsula. They propose that this ancient human individual’s mitochondrial DNA (mtDNA) belongs to haplogroup D1. However, our analysis of postmortem damage patterns finds no evidence for an ancient origin of these sequences. Authors: Kay Prüfer, Matthias Meyer

Prüfer and Meyer raise concerns over the mitochondrial DNA (mtDNA) results we reported for the Hoyo Negro individual, citing failure of a portion of these data to conform to their expectations of ancient DNA (aDNA). Because damage patterns in aDNA vary, outright rejection of our findings on this basis is unwarranted, especially in light of our other observations. Authors: Brian M. Kemp, John Lindo, Deborah A. Bolnick, Ripan S. Malhi, James C. Chatters

For over half a century, the biological roles of nucleic acids as catalytic enzymes, intracellular regulatory molecules, and the carriers of genetic information have been studied extensively. More recently, the sequence-specific binding properties of DNA have been exploited to direct the assembly of materials at the nanoscale. Integral to any methodology focused on assembling matter from smaller pieces is the idea that final structures have well-defined spacings, orientations, and stereo-relationships. This requirement can be met by using DNA-based constructs that present oriented nanoscale bonding elements from rigid core units. Here, we draw analogy between such building blocks and the familiar chemical concepts of “bonds” and “valency” and review two distinct but related strategies that have used this design principle in constructing new configurations of matter. Authors: Matthew R. Jones, Nadrian C. Seeman, Chad A. Mirkin

According to the disease module hypothesis, the cellular components associated with a disease segregate in the same neighborhood of the human interactome, the map of biologically relevant molecular interactions. Yet, given the incompleteness of the interactome and the limited knowledge of disease-associated genes, it is not obvious if the available data have sufficient coverage to map out modules associated with each disease. Here we derive mathematical conditions for the identifiability of disease modules and show that the network-based location of each disease module determines its pathobiological relationship to other diseases. For example, diseases with overlapping network modules show significant coexpression patterns, symptom similarity, and comorbidity, whereas diseases residing in separated network neighborhoods are phenotypically distinct. These tools represent an interactome-based platform to predict molecular commonalities between phenotypically related diseases, even if they do not share primary disease genes. Authors: Jörg Menche, Amitabh Sharma, Maksim Kitsak, Susan Dina Ghiassian, Marc Vidal, Joseph Loscalzo, Albert-László Barabási

Mutations in sunlight-induced melanoma arise from cyclobutane pyrimidine dimers (CPDs), DNA photoproducts that are typically created picoseconds after an ultraviolet (UV) photon is absorbed at thymine or cytosine. We found that in melanocytes, CPDs are generated for >3 hours after exposure to UVA, a major component of the radiation in sunlight and in tanning beds. These “dark CPDs” constitute the majority of CPDs and include the cytosine-containing CPDs that initiate UV-signature C→T mutations. Dark CPDs arise when UV-induced reactive oxygen and nitrogen species combine to excite an electron in fragments of the pigment melanin. This creates a quantum triplet state that has the energy of a UV photon but induces CPDs by energy transfer to DNA in a radiation-independent manner. Melanin may thus be carcinogenic as well as protective against cancer. These findings also validate the long-standing suggestion that chemically generated excited electronic states are relevant to mammalian biology. Authors: Sanjay Premi, Silvia Wallisch, Camila M. Mano, Adam B. Weiner, Antonella Bacchiocchi, Kazumasa Wakamatsu, Etelvino J. H. Bechara, Ruth Halaban, Thierry Douki, Douglas E. Brash

Notch receptors guide mammalian cell fate decisions by engaging the proteins Jagged and Delta-like (DLL). The 2.3 angstrom resolution crystal structure of the interacting regions of the Notch1-DLL4 complex reveals a two-site, antiparallel binding orientation assisted by Notch1 O-linked glycosylation. Notch1 epidermal growth factor–like repeats 11 and 12 interact with the DLL4 Delta/Serrate/Lag-2 (DSL) domain and module at the N-terminus of Notch ligands (MNNL) domains, respectively. Threonine and serine residues on Notch1 are functionalized with O-fucose and O-glucose, which act as surrogate amino acids by making specific, and essential, contacts to residues on DLL4. The elucidation of a direct chemical role for O-glycans in Notch1 ligand engagement demonstrates how, by relying on posttranslational modifications of their ligand binding sites, Notch proteins have linked their functional capacity to developmentally regulated biosynthetic pathways. Authors: Vincent C. Luca, Kevin M. Jude, Nathan W. Pierce, Maxence V. Nachury, Suzanne Fischer, K. Christopher Garcia

Physical systems usually exhibit quantum behavior, such as superpositions and entanglement, only when they are sufficiently decoupled from a lossy environment. Paradoxically, a specially engineered interaction with the environment can become a resource for the generation and protection of quantum states. This notion can be generalized to the confinement of a system into a manifold of quantum states, consisting of all coherent superpositions of multiple stable steady states. We have confined the state of a superconducting resonator to the quantum manifold spanned by two coherent states of opposite phases and have observed a Schrödinger cat state spontaneously squeeze out of vacuum before decaying into a classical mixture. This experiment points toward robustly encoding quantum information in multidimensional steady-state manifolds. Authors: Z. Leghtas, S. Touzard, I. M. Pop, A. Kou, B. Vlastakis, A. Petrenko, K. M. Sliwa, A. Narla, S. Shankar, M. J. Hatridge, M. Reagor, L. Frunzio, R. J. Schoelkopf, M. Mirrahimi, M. H. Devoret

That the speed of light in free space is constant is a cornerstone of modern physics. However, light beams have finite transverse size, which leads to a modification of their wave vectors resulting in a change to their phase and group velocities. We study the group velocity of single photons by measuring a change in their arrival time that results from changing the beam’s transverse spatial structure. Using time-correlated photon pairs, we show a reduction in the group velocity of photons in both a Bessel beam and photons in a focused Gaussian beam. In both cases, the delay is several micrometers over a propagation distance of ~1 meter. Our work highlights that, even in free space, the invariance of the speed of light only applies to plane waves. Authors: Daniel Giovannini, Jacquiline Romero, Václav Potoček, Gergely Ferenczi, Fiona Speirits, Stephen M. Barnett, Daniele Faccio, Miles J. Padgett

The evolution of galaxies is connected to the growth of supermassive black holes in their centers. During the quasar phase, a huge luminosity is released as matter falls onto the black hole, and radiation-driven winds can transfer most of this energy back to the host galaxy. Over five different epochs, we detected the signatures of a nearly spherical stream of highly ionized gas in the broadband x-ray spectra of the luminous quasar PDS 456. This persistent wind is expelled at relativistic speeds from the inner accretion disk, and its wide aperture suggests an effective coupling with the ambient gas. The outflow’s kinetic power larger than 1046 ergs per second is enough to provide the feedback required by models of black hole and host galaxy coevolution. Authors: E. Nardini, J. N. Reeves, J. Gofford, F. A. Harrison, G. Risaliti, V. Braito, M. T. Costa, G. A. Matzeu, D. J. Walton, E. Behar, S. E. Boggs, F. E. Christensen, W. W. Craig, C. J. Hailey, G. Matt, J. M. Miller, P. T. O’Brien, D. Stern, T. J. Turner, M. J. Ward

The fleeting lifetimes of the transition states (TSs) of chemical reactions make determination of their three-dimensional structures by diffraction methods a challenge. Here, we used packing interactions within the core of a protein to stabilize the planar TS conformation for rotation around the central carbon-carbon bond of biphenyl so that it could be directly observed by x-ray crystallography. The computational protein design software Rosetta was used to design a pocket within threonyl-transfer RNA synthetase from the thermophile Pyrococcus abyssi that forms complementary van der Waals interactions with a planar biphenyl. This latter moiety was introduced biosynthetically as the side chain of the noncanonical amino acid p-biphenylalanine. Through iterative rounds of computational design and structural analysis, we identified a protein in which the side chain of p-biphenylalanine is trapped in the energetically disfavored, coplanar conformation of the TS of the bond rotation reaction. Authors: Aaron D. Pearson, Jeremy H. Mills, Yifan Song, Fariborz Nasertorabi, Gye Won Han, David Baker, Raymond C. Stevens, Peter G. Schultz

Cope’s rule proposes that animal lineages evolve toward larger body size over time. To test this hypothesis across all marine animals, we compiled a data set of body sizes for 17,208 genera of marine animals spanning the past 542 million years. Mean biovolume across genera has increased by a factor of 150 since the Cambrian, whereas minimum biovolume has decreased by less than a factor of 10, and maximum biovolume has increased by more than a factor of 100,000. Neutral drift from a small initial value cannot explain this pattern. Instead, most of the size increase reflects differential diversification across classes, indicating that the pattern does not reflect a simple scaling-up of widespread and persistent selection for larger size within populations. Authors: Noel A. Heim, Matthew L. Knope, Ellen K. Schaal, Steve C. Wang, Jonathan L. Payne

Navigation depends on multiple neural systems that encode the moment-to-moment changes in an animal’s direction and location in space. These include head direction (HD) cells representing the orientation of the head and grid cells that fire at multiple locations, forming a repeating hexagonal grid pattern. Computational models hypothesize that generation of the grid cell signal relies upon HD information that ascends to the hippocampal network via the anterior thalamic nuclei (ATN). We inactivated or lesioned the ATN and subsequently recorded single units in the entorhinal cortex and parasubiculum. ATN manipulation significantly disrupted grid and HD cell characteristics while sparing theta rhythmicity in these regions. These results indicate that the HD signal via the ATN is necessary for the generation and function of grid cell activity. Authors: Shawn S. Winter, Benjamin J. Clark, Jeffrey S. Taube

An important question in ecology is how mechanistic processes occurring among individuals drive large-scale patterns of community formation and change. Here we show that in two species of bluebirds, cycles of replacement of one by the other emerge as an indirect consequence of maternal influence on offspring behavior in response to local resource availability. Sampling across broad temporal and spatial scales, we found that western bluebirds, the more competitive species, bias the birth order of offspring by sex in a way that influences offspring aggression and dispersal, setting the stage for rapid increases in population density that ultimately result in the replacement of their sister species. Our results provide insight into how predictable community dynamics can occur despite the contingency of local behavioral interactions. Authors: Renée A. Duckworth, Virginia Belloni, Samantha R. Anderson

Pancreatic β cells lower insulin release in response to nutrient depletion. The question of whether starved β cells induce macroautophagy, a predominant mechanism maintaining energy homeostasis, remains poorly explored. We found that, in contrast to many mammalian cells, macroautophagy in pancreatic β cells was suppressed upon starvation. Instead, starved β cells induced lysosomal degradation of nascent secretory insulin granules, which was controlled by protein kinase D (PKD), a key player in secretory granule biogenesis. Starvation-induced nascent granule degradation triggered lysosomal recruitment and activation of mechanistic target of rapamycin that suppressed macroautophagy. Switching from macroautophagy to insulin granule degradation was important to keep insulin secretion low upon fasting. Thus, β cells use a PKD-dependent mechanism to adapt to nutrient availability and couple autophagy flux to secretory function. Authors: Alexander Goginashvili, Zhirong Zhang, Eric Erbs, Coralie Spiegelhalter, Pascal Kessler, Michael Mihlan, Adrien Pasquier, Ksenia Krupina, Nicole Schieber, Laura Cinque, Joëlle Morvan, Izabela Sumara, Yannick Schwab, Carmine Settembre, Romeo Ricci

Macromolecular function is rooted in energy landscapes, where sequence determines not a single structure but an ensemble of conformations. Hence, evolution modifies a protein’s function by altering its energy landscape. Here, we recreate the evolutionary pathway between two modern human oncogenes, Src and Abl, by reconstructing their common ancestors. Our evolutionary reconstruction combined with x-ray structures of the common ancestor and pre–steady-state kinetics reveals a detailed atomistic mechanism for selectivity of the successful cancer drug Gleevec. Gleevec affinity is gained during the evolutionary trajectory toward Abl and lost toward Src, primarily by shifting an induced-fit equilibrium that is also disrupted in the clinical T315I resistance mutation. This work reveals the mechanism of Gleevec specificity while offering insights into how energy landscapes evolve. Authors: C. Wilson, R. V. Agafonov, M. Hoemberger, S. Kutter, A. Zorba, J. Halpin, V. Buosi, R. Otten, D. Waterman, D. L. Theobald, D. Kern

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

The 2015 Gordon Research Conference schedule was published on pages 888 to 912 of this issue of the print version of Science. The current schedule can also be found online at www.grc.org/.

We are not paying enough attention to the world's soils, a “nearly forgotten resource” and our “silent ally,” 33% of which are in a state of degradation.* We can't breathe, eat, drink, or be healthy without sustainably managing soils. So in recognizing 2015 as the International Year of Soils, the United Nations (UN) is focusing global attention on the increasing pressures on soils and their ripple effect on other global challenges. Authors: Diana H. Wall, Johan Six

In science news around the world, the Institute of Medicine gives chronic fatigue syndrome a new name and recommends new diagnostics, the National Synchrotron Light Source II is dedicated, a National Institutes of Health idea to create an "emeritus award" for aging scientists is panned in the blogosphere, a South Korean newspaper reports that disgraced stem cell scientist Woo Suk Hwang is teaming up with respected researcher Shoukhrat Mitalipov on a new venture to work on cloning mechanisms, the U.S. Department of Energy pulls out of the country's planned first commercial-scale carbon capture and storage plant, and a just-released report details the reasoning behind three judges' decision to acquit six Italian scientists of manslaughter for failing to warn the public of the L'Aquila earthquake. Also, the U.S. Congress pushes for greater protections for farm animals in scientific research. And a "shattered" chromosome cures a woman born with a serious genetic disease.

The fierce public relations war over genetically modified (GM) food has a new front. A nonprofit group opposed to GM products late last month filed a flurry of freedom of information requests with at least four U.S. universities, asking administrators to turn over any correspondence between a dozen academic researchers and a handful of agricultural companies, trade groups, and public relations firms. The scientists—many of whom have publicly supported agricultural biotechnologies—are debating how best to respond, and at least one university has already rejected the request. The group, U.S. Right to Know (USRTK) of Oakland, California, says it targeted only researchers who have written articles posted on GMO Answers, a website backed by food and biotechnology firms, and work in states with laws that require public institutions to share many internal documents on request. USRTK is interested in documenting links between universities and business and is "especially looking to learn how these faculty members have been appropriated into the PR machine for the chemical-agro industry," says Executive Director Gary Ruskin. Author: Keith Kloor

A fatal virus is felling pandas at a breeding center in China, prompting authorities to institute strict quarantine and disease control measures. State media report that four pandas have died, the latest on 4 February. Officials are blaming canine distemper, a highly contagious virus often spread by dogs that in recent years has taken a heavy toll on lions, seals, and other mammals. The cases have rattled panda researchers at a time when they are still waiting for the release of figures from China's fourth national panda survey, expected months ago. The deaths have also exposed concerns that China is overemphasizing captive breeding at the expense of conserving the animals' remaining wild habitat in the mountains of western China. Author: Mara Hvistendahl

News leaked last week that the drug favipiravir worked in some Ebola patients, but even researchers running the study in Guinea said questions remain about its efficacy. Interpreting the data is difficult because there is no control arm that treated patients can be compared with. This is just one of several confusing twists in the search for a treatment that can stave off death and disease from Ebola virus. Chimerix, the maker of an antiviral called brincidofovir, surprised investigators in Liberia when it suddenly ended a study of its drug after discussions with the U.S. Food and Drug Administration. Chimerix noted that the study was having trouble enrolling patients because Liberia has seen a steep drop in cases, but the researchers running it said they had hoped to expand the trial to Sierra Leone, where most new infections are happening. Liberia is also beginning another trial with ZMapp, a cocktail of Ebola antibodies, and study leaders are having difficulty convincing Sierra Leone and Guinea to join because the study uses a placebo control. Finally, a trial of convalescent serum taken from recovered patients is getting under way in Guinea, but there are now questions about whether it should be compared with favipiravir as a control. Authors: Kai Kupferschmidt, Jon Cohen

The United Nations is developing a list of Sustainable Development Goals, which are intended to guide efforts to reduce poverty and improve well-being by 2030 while protecting the planet. The 17 goals include 169 targets to measure progress. But in a comprehensive review, scientists say the many targets must be clarified and quantified. Many lack specific endpoints and time frames or can't be measured. The problem with vague goals, experts say, is that they allow too much wiggle room in evaluating progress. It is not clear how much the draft targets will be changed before they are finalized at a summit in September. Author: Erik Stokstad

China raises and consumes roughly half the planet's pigs, which produce an estimated 618 billion kilograms of manure each year. And the pigs consume and excrete tens of thousands of tons of antibiotics, added to their feed to keep them healthy and promote growth. Recent studies, including one due out soon, are documenting the predictable result: a proliferation in China's watercourses of bacteria containing genes for resistance to antibiotics. It's a phenomenon familiar to other countries with industrialized meat systems, but on a whole new scale. A chief worry is that antibiotic resistance genes could find their way into pathogenic bacteria, creating so-called superbugs. Author: Christina Larson

Severe, decades-long "megadroughts" that hit the southwestern and midwestern United States over the past millennium may be just a preview of droughts to come in the next century as a result of climate change, new research suggests. According to a new analysis of 17 state-of-the-art climate models and reconstructions of historical drought based on 1000 years of tree-ring data, the regions are heading into a period of unprecedented dryness even if CO2 emissions are dramatically reduced. Under a "business-as-usual" emission scenario, there's an 80% likelihood that at least one decades-long megadrought will hit the regions between 2050 and 2100, scientists say. Author: Emily Underwood

A spate of recent findings is beginning to unravel the mystery surrounding the earliest pioneers of the harsh, low-oxygen Tibetan Plateau. Archaeological evidence shows that nomads wandered up river valleys almost as soon as modern humans arrived in Asia. They came not just from the east—the Chinese heartland—but from the west and south as well. But which of those groups finally settled on the "roof of the world" and became the present-day Tibetans? Like many questions of geography and migration, this one has political overtones. Seeking the high ground in disputes about Tibet's historical relationship to China, the Chinese government has seized on recent findings that Tibetans and Han Chinese may have descended from a common ancestor, diverging only in the past several thousand years. Evidence points to a complex and nuanced picture, suggesting that the nomads who ventured onto the plateau thousands of years earlier, from all across Asia, left a substantial genetic imprint on today's Tibetans. Author: Jane Qiu

To perform such mechanically demanding tasks as biting, chewing, or even rock-grinding, animal teeth have evolved into a wide range of morphologies, constructed from minerals as diverse as magnetite, calcium carbonate, and carbonated hydroxy-apatite. Moreover, serial tooth replacement or continuously growing teeth with self-sharpening abilities have evolved in many vertebrates and invertebrates to counteract the effects of constant abrasion (see the figure). On page 746 of this issue, Gordon et al. (1) use rodent and rabbit tooth enamel as model systems, combining atomic resolution tomography and x-ray spectroscopy to elucidate the nanoscale architecture of this high-performance biological ceramic. Authors: Yael Politi, James C. Weaver

Transcription factors form multiprotein complexes that coordinate gene expression and regulate cellular responses (1). In cancer, aberrantly expressed transcription factors often alter gene expression programs, and although these transcription factors are promising targets for therapeutics (2), they remain largely untested. Deemed “undruggable” (3), their perturbation often requires specific disruption of protein-protein or protein-DNA interactions. To date, the discovery or design of small-molecule probes and drugs that specifically disrupt such interactions has proved challenging. On page 779 of this issue, Illendula et al. (4) describe the development of a small molecule that inhibits progression of a subtype of acute myeloid leukemia (AML). The compound binds to an oncogenic version of a transcription factor subunit called core binding factor β (CBFβ), which arises from a chromosomal translocation. The strategy used to develop this drug may be applicable to other oncogenic proteins that arise from chromosomal translocation events. Authors: Andrew Chen, Angela N. Koehler

RNA viruses are a ubiquitous class of pathogens that cause serious human, animal, and plant disease. To synthesize new viral genomes in infected hosts, RNA viruses encode special enzymes, RNA-dependent RNA polymerases (RdRps), which are thus prime targets for antiviral drug design. A case study is hepatitis C virus (HCV). HCV is a major human pathogen that chronically infects an estimated 170 million people worldwide, greatly increasing risk of developing life-threatening liver disease, including cirrhosis and cancer. New drugs against HCV have recently come to market that are extremely successful compared to the former standard of care and allow cure (that is, eradication of HCV from the patient) in over 95% of cases (1). Foremost among these new drugs is sofosbuvir, a nucleoside inhibitor targeting the active site of the HCV RdRp, NS5B. On page 771 of this issue, Appleby et al. describe new crystal structures of HCV NS5B (2) that are a major advance both in our basic understanding of RdRp activity and in the way sofosbuvir can inhibit HCV replication. Author: Stéphane Bressanelli

Many drugs must be absorbed into the circulation for medicinal effects to occur at the intended sites of action, and so a holy grail of drug delivery is to improve the passage of pharmaceuticals across tissue barriers. Most oral drugs are absorbed in the small intestine, where the lumen is lined with epithelial cells. Thus, new therapeutic strategies for efficient oral delivery can benefit from a better understanding of the protein complexes, such as the tight junction, that maintain the integrity of this epithelium. On page 775 of this issue, Saitoh et al. (1) report the structure of a tight junction constituent called claudin-19, bound to a bacterial toxin called Clostridium perfringens enterotoxin (CPE), an agent that disrupts tight junctions and is a major cause of foodborne illness by this pathogen. The structural information may be useful in developing specific claudin-targeted compounds that improve drug delivery across tissue barriers that currently limit drug absorption. Authors: Per Artursson, Stefan D. Knight