The range of fault slip behaviors near the trench at subduction plate boundaries is critical to know, as this is where the world’s largest, most damaging tsunamis are generated. Our knowledge of these behaviors has remained largely incomplete, partially due to the challenging nature of crustal deformation measurements at offshore plate boundaries. Here we present detailed seafloor deformation observations made during an offshore slow-slip event (SSE) in September and October 2014, using a network of absolute pressure gauges deployed at the Hikurangi subduction margin offshore New Zealand. These data show the distribution of vertical seafloor deformation during the SSE and reveal direct evidence for SSEs occurring close to the trench (within 2 kilometers of the seafloor), where very low temperatures and pressures exist.
Authors: Laura M. Wallace, Spahr C. Webb, Yoshihiro Ito, Kimihiro Mochizuki, Ryota Hino, Stuart Henrys, Susan Y. Schwartz, Anne F. Sheehan
Magnetotactic bacteria perform biomineralization of intracellular magnetite (Fe3O4) nanoparticles. Although they may be among the earliest microorganisms capable of biomineralization on Earth, identifying their activity in ancient sedimentary rocks remains challenging because of the lack of a reliable biosignature. We determined Fe isotope fractionations by the magnetotactic bacterium Magnetospirillum magneticum AMB-1. The AMB-1 strain produced magnetite strongly depleted in heavy Fe isotopes, by 1.5 to 2.5 per mil relative to the initial growth medium. Moreover, we observed mass-independent isotope fractionations in 57Fe during magnetite biomineralization but not in even Fe isotopes (54Fe, 56Fe, and 58Fe), highlighting a magnetic isotope effect. This Fe isotope anomaly provides a potential biosignature for the identification of magnetite produced by magnetotactic bacteria in the geological record.
Authors: Matthieu Amor, Vincent Busigny, Pascale Louvat, Alexandre Gélabert, Pierre Cartigny, Mickaël Durand-Dubief, Georges Ona-Nguema, Edouard Alphandéry, Imène Chebbi, François Guyot
Many recent studies point to increasing inequality in mortality in the United States over the past 20 years. These studies often use mortality rates in middle and old age. We used poverty level rankings of groups of U.S. counties as a basis for analyzing inequality in mortality for all age groups in 1990, 2000, and 2010. Consistent with previous studies, we found increasing inequality in mortality at older ages. For children and young adults below age 20, however, we found strong mortality improvements that were most pronounced in poorer counties, implying a strong decrease in mortality inequality. These younger cohorts will form the future adult U.S. population, so this research suggests that inequality in old-age mortality is likely to decline.
Authors: J. Currie, H. Schwandt
Synapse loss in Alzheimer’s disease (AD) correlates with cognitive decline. Involvement of microglia and complement in AD has been attributed to neuroinflammation, prominent late in disease. Here we show in mouse models that complement and microglia mediate synaptic loss early in AD. C1q, the initiating protein of the classical complement cascade, is increased and associated with synapses before overt plaque deposition. Inhibition of C1q, C3, or the microglial complement receptor CR3 reduces the number of phagocytic microglia, as well as the extent of early synapse loss. C1q is necessary for the toxic effects of soluble β-amyloid (Aβ) oligomers on synapses and hippocampal long-term potentiation. Finally, microglia in adult brains engulf synaptic material in a CR3-dependent process when exposed to soluble Aβ oligomers. Together, these findings suggest that the complement-dependent pathway and microglia that prune excess synapses in development are inappropriately activated and mediate synapse loss in AD.
Authors: Soyon Hong, Victoria F. Beja-Glasser, Bianca M. Nfonoyim, Arnaud Frouin, Shaomin Li, Saranya Ramakrishnan, Katherine M. Merry, Qiaoqiao Shi, Arnon Rosenthal, Ben A. Barres, Cynthia A. Lemere, Dennis J. Selkoe, Beth Stevens
Different combinations of histone modifications have been proposed to signal distinct gene regulatory functions, but this area is poorly addressed by existing technologies. We applied high-throughput single-molecule imaging to decode combinatorial modifications on millions of individual nucleosomes from pluripotent stem cells and lineage-committed cells. We identified definitively bivalent nucleosomes with concomitant repressive and activating marks, as well as other combinatorial modification states whose prevalence varies with developmental potency. We showed that genetic and chemical perturbations of chromatin enzymes preferentially affect nucleosomes harboring specific modification states. Last, we combined this proteomic platform with single-molecule DNA sequencing technology to simultaneously determine the modification states and genomic positions of individual nucleosomes. This single-molecule technology has the potential to address fundamental questions in chromatin biology and epigenetic regulation.
Authors: Efrat Shema, Daniel Jones, Noam Shoresh, Laura Donohue, Oren Ram, Bradley E. Bernstein
A variety of organisms have evolved mechanisms to detect and respond to light, in which the response is mediated by protein structural changes after photon absorption. The initial step is often the photoisomerization of a conjugated chromophore. Isomerization occurs on ultrafast time scales and is substantially influenced by the chromophore environment. Here we identify structural changes associated with the earliest steps in the trans-to-cis isomerization of the chromophore in photoactive yellow protein. Femtosecond hard x-ray pulses emitted by the Linac Coherent Light Source were used to conduct time-resolved serial femtosecond crystallography on photoactive yellow protein microcrystals over a time range from 100 femtoseconds to 3 picoseconds to determine the structural dynamics of the photoisomerization reaction.
Authors: Kanupriya Pande, Christopher D. M. Hutchison, Gerrit Groenhof, Andy Aquila, Josef S. Robinson, Jason Tenboer, Shibom Basu, Sébastien Boutet, Daniel P. DePonte, Mengning Liang, Thomas A. White, Nadia A. Zatsepin, Oleksandr Yefanov, Dmitry Morozov, Dominik Oberthuer, Cornelius Gati, Ganesh Subramanian, Daniel James, Yun Zhao, Jake Koralek, Jennifer Brayshaw, Christopher Kupitz, Chelsie Conrad, Shatabdi Roy-Chowdhury, Jesse D. Coe, Markus Metz, Paulraj Lourdu Xavier, Thomas D. Grant, Jason E. Koglin, Gihan Ketawala, Raimund Fromme, Vukica Šrajer, Robert Henning, John C. H. Spence, Abbas Ourmazd, Peter Schwander, Uwe Weierstall, Matthias Frank, Petra Fromme, Anton Barty, Henry N. Chapman, Keith Moffat, Jasper J. van Thor, Marius Schmidt
A weekly roundup of information on newly offered instrumentation, apparatus, and laboratory materials of potential interest to researchers.
The CRISPR/Cas9 system allows for unprecedented ease and control when editing the genome. Its potential impact on drug discovery is vast, including enabling gene and cell replacement therapies, identifying novel drug targets through functional genomic screens, and simplifying the production of disease models using permanent knockouts for validating therapy targets and testing drug efficacy. But in practical terms, how is CRISPR/Cas9 currently being applied, and where might the future challenges and pitfalls be? Furthermore, how do assays based on the new CRISPR/Cas9 technology compare with current screening methodologies, particularly those using small interfering RNA (siRNA)?View the Webinar
Authors: Lorenz Mayr, Ralph Garippa
Author: Yevgeniya Nusinovich
Author: Stella M. Hurtley
Author: Nicholas S. Wigginton
Author: Melissa McCartney
The primary function of the genome is to store, propagate, and express the genetic information that gives rise to a cell’s architectural and functional machinery. However, the genome is also a major structural component of the cell. Besides its genetic roles, the genome affects cellular functions by nongenetic means through its physical and structural properties, particularly by exerting mechanical forces and by serving as a scaffold for binding of cellular components. Major cellular processes affected by nongenetic functions of the genome include establishment of nuclear structure, signal transduction, mechanoresponses, cell migration, and vision in nocturnal animals. We discuss the concept, mechanisms, and implications of nongenetic functions of the genome.
Authors: Michael Bustin, Tom Misteli
Heterozygous SHANK3 mutations are associated with idiopathic autism and Phelan-McDermid syndrome. SHANK3 is a ubiquitously expressed scaffolding protein that is enriched in postsynaptic excitatory synapses. Here, we used engineered conditional mutations in human neurons and found that heterozygous and homozygous SHANK3 mutations severely and specifically impaired hyperpolarization-activated cation (Ih) channels. SHANK3 mutations caused alterations in neuronal morphology and synaptic connectivity; chronic pharmacological blockage of Ih channels reproduced these phenotypes, suggesting that they may be secondary to Ih-channel impairment. Moreover, mouse Shank3-deficient neurons also exhibited severe decreases in Ih currents. SHANK3 protein interacted with hyperpolarization-activated cyclic nucleotide-gated channel proteins (HCN proteins) that form Ih channels, indicating that SHANK3 functions to organize HCN channels. Our data suggest that SHANK3 mutations predispose to autism, at least partially, by inducing an Ih channelopathy that may be amenable to pharmacological intervention.
Authors: Fei Yi, Tamas Danko, Salome Calado Botelho, Christopher Patzke, ChangHui Pak, Marius Wernig, Thomas C. Südhof
Profound environmental and faunal changes are associated with climatic deterioration during the Eocene-Oligocene transition (EOT) roughly 34 million years ago. Reconstructing how Asian primates responded to the EOT has been hindered by a sparse record of Oligocene primates on that continent. Here, we report the discovery of a diverse primate fauna from the early Oligocene of southern China. In marked contrast to Afro-Arabian Oligocene primate faunas, this Asian fauna is dominated by strepsirhines. There appears to be a strong break between Paleogene and Neogene Asian anthropoid assemblages. Asian and Afro-Arabian primate faunas responded differently to EOT climatic deterioration, indicating that the EOT functioned as a critical evolutionary filter constraining the subsequent course of primate evolution across the Old World.
Authors: Xijun Ni, Qiang Li, Lüzhou Li, K. Christopher Beard
In nature, structural specificity in DNA and proteins is encoded differently: In DNA, specificity arises from modular hydrogen bonds in the core of the double helix, whereas in proteins, specificity arises largely from buried hydrophobic packing complemented by irregular peripheral polar interactions. Here, we describe a general approach for designing a wide range of protein homo-oligomers with specificity determined by modular arrays of central hydrogen-bond networks. We use the approach to design dimers, trimers, and tetramers consisting of two concentric rings of helices, including previously not seen triangular, square, and supercoiled topologies. X-ray crystallography confirms that the structures overall, and the hydrogen-bond networks in particular, are nearly identical to the design models, and the networks confer interaction specificity in vivo. The ability to design extensive hydrogen-bond networks with atomic accuracy enables the programming of protein interaction specificity for a broad range of synthetic biology applications; more generally, our results demonstrate that, even with the tremendous diversity observed in nature, there are fundamentally new modes of interaction to be discovered in proteins.
Authors: Scott E. Boyken, Zibo Chen, Benjamin Groves, Robert A. Langan, Gustav Oberdorfer, Alex Ford, Jason M. Gilmore, Chunfu Xu, Frank DiMaio, Jose Henrique Pereira, Banumathi Sankaran, Georg Seelig, Peter H. Zwart, David Baker
Natural recombination combines pieces of preexisting proteins to create new tertiary structures and functions. We describe a computational protocol, called SEWING, which is inspired by this process and builds new proteins from connected or disconnected pieces of existing structures. Helical proteins designed with SEWING contain structural features absent from other de novo designed proteins and, in some cases, remain folded at more than 100°C. High-resolution structures of the designed proteins CA01 and DA05R1 were solved by x-ray crystallography (2.2 angstrom resolution) and nuclear magnetic resonance, respectively, and there was excellent agreement with the design models. This method provides a new strategy to rapidly create large numbers of diverse and designable protein scaffolds.
Authors: T. M. Jacobs, B. Williams, T. Williams, X. Xu, A. Eletsky, J. F. Federizon, T. Szyperski, B. Kuhlman
In chemical synthesis, rapid intramolecular rearrangements often foil attempts at site-selective bimolecular functionalization. We developed a microfluidic technique that outpaces the very rapid anionic Fries rearrangement to chemoselectively functionalize iodophenyl carbamates at the ortho position. Central to the technique is a chip microreactor of our design, which can deliver a reaction time in the submillisecond range even at cryogenic temperatures. The microreactor was applied to the synthesis of afesal, a bioactive molecule exhibiting anthelmintic activity, to demonstrate its potential for practical synthesis and production.
Authors: Heejin Kim, Kyoung-Ik Min, Keita Inoue, Do Jin Im, Dong-Pyo Kim, Jun-ichi Yoshida
We may not be raring to go on a Monday morning, but humans are the Energizer Bunnies of the primate world. That's the conclusion of a new study that for the first time measures precisely how many calories humans and apes burn each day. Compared with chimpanzees and other apes, our revved-up internal engines burn calories 27% faster, according to a paper in Nature this week. This higher metabolic rate equips us to quickly fuel energy-hungry brain cells, paving the way for our bigger brains. And lest we run out of gas when food is short, the study also found that humans are fatter than other primates, giving us energy stores to draw on in lean times.
Author: Ann Gibbons
Researchers studying human embryos in the lab have always hit a roadblock at about 7 days—the point where the embryo would usually attach to the uterus. Now, two teams report growing human embryos about a week past that point, revealing key differences between the development of human and mice embryos. The limit now isn't technological, but ethical: a widely held rule that dictates all embryo research should be stopped at 14 days. Now that culturing methods have finally made it possible to reach this point, some scientists and bioethicists are saying the rule should be revisited. But that won't be welcomed by those who consider the rule to have a firm moral grounding—nor by those who oppose all research on human embryos.
Author: Patrick Monahan
How do you retire a 5-ton whale? That's a question some advocates and scientists have been asking themselves in the wake of SeaWorld's historic decision in March to stop breeding the 29 orcas in its care. Now, a new organization of about three dozen scientists, marine veterinarians, and engineers called the Whale Sanctuary Project has begun developing plans for an orca sanctuary, including coves and small groups of islands that could be cordoned off. But critics say that placing an orca that has spent its entire life in a sterile, concrete tank into an ocean filled with creatures and conditions it has never encountered before could be dangerous not just for the whale, but for the previously whale-free ecosystem. Plus, the costs are mammoth—perhaps tens or hundreds of millions of dollars.
Author: David Grimm
To a birdwatcher or pet owner, it may be obvious that individual animals have distinct personalities. However, that idea has been slow to penetrate biology. Yet now researchers are learning that just as human quirks and temperaments shape our lives and the world around us, the behavior patterns of individual animals affect their role in their ecosystem, their prospects for survival, and, ultimately, their evolution. Researchers have figured out how to quantify personality and are showing in studies of great tits, salamanders, stickleback fish, lizards, and social spiders why different personalities persist, how they might lead to speciation, and the role they might play in the spread of information and disease.
Author: Elizabeth Pennisi
Over the past decade, scientists have made exciting progress in designing protein folds entirely on the computer and then successfully synthesizing them in the laboratory (1–5). These designer proteins had the same structure in experiment as in the model and were very stable; however, they lacked important structural features seen in protein interfaces and enzyme active sites. In two reports on pages 680 and 687 of this issue, Boyken et al. (6) and Jacobs et al. (7) use the Rosetta biomolecular modeling software to design proteins that include some of these features. Experiments show that these new designs retain high structural precision and stability.
Authors: Ravit Netzer, Sarel J. Fleishman
The impact of cancer immunotherapy on clinical cancer care is growing rapidly. However, different immunotherapies remedy distinct problems in cancer–immune system interactions. What would be the most effective therapy for an individual patient? Here, a framework is proposed for describing the different interactions between cancer and the immune system in individual cases, with the aim to focus biomarker research and to help guide treatment choice.
Authors: Christian U. Blank, John B. Haanen, Antoni Ribas, Ton N. Schumacher
A deluge of recent studies has shown that poorer communities suffer worse health outcomes. Among low-income Americans, life expectancy at age 40 in the poorest areas of the U.S. is 4.5 years lower than in the highest-income areas (1). In 2010, infant mortality rates in the poorest U.S. communities were over 70% higher than those in the most affluent ones [see tables S3 and S4 in (2)]. On page 708 of this issue, Currie and Schwandt paint a more complicated but encouraging picture (2). They show that, despite rising inequality in almost every dimension of American life, the child mortality gap between the poorest and the richest counties has shrunk in recent decades.
Authors: Martha J. Bailey, Brenden Timpe
Concerns have been raised about labor market imbalances that see a growing number of postdoctoral researchers pursuing a limited number of faculty positions (1–4). Proposed demand-side solutions include capping the duration of postdoc training or hiring more permanent staff scientists (1, 4, 5). Others focus on the supply side, arguing that Ph.D.'s need better information about labor market conditions and nonacademic career options (4, 6, 7). Unfortunately, it is not clear why Ph.D. students pursue postdoc positions and how their plans depend on individual-level factors, such as career goals or labor market perceptions. We describe evidence of a “default” postdoc and of “holding patterns” that suggest a need for increased attention to career planning among students, their mentors, graduate schools, and funders.
Authors: Henry Sauermann, Michael Roach
Authors: Noboru Takamura, Makiko Orita, Shunichi Yamashita, Rethy Chhem
Authors: Makoto Miyazaki, Koichi Tanigawa, Michio Murakami
Authors: Sanae Midorikawa, Satoru Suzuki, Akira Ohtsuru
We described a lithium-oxygen (Li-O2) battery comprising a graphene electrode, a dimethoxyethane-based electrolyte, and H2O and lithium iodide (LiI) additives, lithium hydroxide (LiOH) being the predominant discharge product. We demonstrate, in contrast to the work of Shen et al., that the chemical reactivity between LiOH and the triiodide ion (I3–) to form IO3– indicates that LiOH can be removed on charging; the electrodes do not clog, even after multiple cycles, confirming that solid products are reversibly removed.
Authors: Tao Liu, Gunwoo Kim, Javier Carretero-González, Elizabeth Castillo-Martínez, Clare P. Grey
[Errata] Erratum for the Report “Network of epistatic interactions within a yeast snoRNA” by O. Puchta, B. Cseke, H. Czaja, D. Tollervey, G. Sanguinetti, G. Kudla
[Errata] Erratum for the Research Article “The TopoVIB-Like protein family is required for meiotic DNA double-strand break formation” by T. Robert, A. Nore, C. Brun, C. Maffre, B. Crimi, V. Guichard,* H.-M. Bourbon, B. de Massy
The United Kingdom has ample resources for ocean energy and has long been a leader in wave energy research. After the bankruptcies of two pioneering wave energy companies, the Scottish government has gone back to the drawing board. A new agency is funding crosscutting research, for example in materials and control systems, that could help a range of wave energy devices. The government program is also trying to improve technology transfer and build investor confidence by benchmarking progress. Companies are trying out novel designs, such as a giant rubber tube and polymers that generate electricity when flexed. Another goal is to help devices submerge to avoid dangerous waves.
Author: Erik Stokstad