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Attack on amyloid-β protein p.36

An antibody therapy markedly reduces aggregates of amyloid-β, the hallmark protein of Alzheimer's disease, and might slow cognitive decline in patients. Confirmation of a cognitive benefit would be a game-changer. See Article p.50

Eric M. Reiman

doi: 10.1038/537036a

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Cometary dust under the microscope p.37

The Rosetta spacecraft made history by successfully orbiting a comet. Data from the craft now reveal the structure of the comet's dust particles, shedding light on the processes that form planetary systems. See Letter p.73

Ludmilla Kolokolova

doi: 10.1038/537037a

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Moulding the ribosome p.38

Production of the cell's translational apparatus, the ribosome, requires the orchestrated function of hundreds of proteins. A structure of its earliest precursor yields unprecedented insight into ribosome formation.

Marlene Oeffinger

doi: 10.1038/537038a

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Southern Ocean freshened by sea ice p.40

The Southern Ocean has become less salty during the past few decades. An analysis of sea-ice transport in the ocean suggests that this phenomenon can be explained by coupled changes in sea-ice drift and thickness. See Letter p.89

Ted Maksym

doi: 10.1038/537040a

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Suffocation of gene expression p.42

If a tumour outgrows its blood supply, oxygen levels in its cells decrease. It emerges that this change can alter gene expression by limiting the activity of TET enzymes, which remove methyl groups from DNA. See Article p.63

Dan Ye & Yue Xiong

doi: 10.1038/nature19426

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Muddy messages about American migration p.43

When and by which paths did early humans migrate into America? An analysis of ancient plant and animal remains revises the timeframe during which a route may have opened between ice sheets in northwest America. See Article p.45

Suzanne McGowan

doi: 10.1038/nature19421

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Articles

Postglacial viability and colonization in North America’s ice-free corridor p.45

During much of the last ice age, continental ice sheets prevented humans from migrating into North America from Siberia; an environmental reconstruction of the corridor that opened up between the Cordilleran and Laurentide ice sheets reveals that it would have been inhospitable to the initial colonizing humans, who therefore probably entered North America by a different route.

Mikkel W. Pedersen, Anthony Ruter, Charles Schweger, Harvey Friebe, Richard A. Staff, Kristian K. Kjeldsen, Marie L. Z. Mendoza, Alwynne B. Beaudoin, Cynthia Zutter, Nicolaj K. Larsen + et al.

doi: 10.1038/nature19085

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The antibody aducanumab reduces Aβ plaques in Alzheimer’s disease p.50

Aducanumab, a human monoclonal antibody that selectively targets aggregated Aβ, reduces soluble and insoluble Aβ in the brain, an action accompanied by a dose-dependent slowing of clinical decline in treated patients.

Jeff Sevigny, Ping Chiao, Thierry Bussière, Paul H. Weinreb, Leslie Williams, Marcel Maier, Robert Dunstan, Stephen Salloway, Tianle Chen, Yan Ling + et al.

doi: 10.1038/nature19323

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A developmental coordinate of pluripotency among mice, monkeys and humans p.57

Using a single-cell sequencing analysis in monkey embryos, and comparing the genes expressed during early development in this species with those in mice and in human pluripotent stem cells, the authors define characteristics of pluripotency ontogeny across mammalian species.

Tomonori Nakamura, Ikuhiro Okamoto, Kotaro Sasaki, Yukihiro Yabuta, Chizuru Iwatani, Hideaki Tsuchiya, Yasunari Seita, Shinichiro Nakamura, Takuya Yamamoto & Mitinori Saitou

doi: 10.1038/nature19096

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Tumour hypoxia causes DNA hypermethylation by reducing TET activity p.63

Hypoxia in solid tumours reduces the expression of tumour suppressor genes through an epigenetic mechanism.

Bernard Thienpont, Jessica Steinbacher, Hui Zhao, Flora D’Anna, Anna Kuchnio, Athanasios Ploumakis, Bart Ghesquière, Laurien Van Dyck, Bram Boeckx, Luc Schoonjans + et al.

doi: 10.1038/nature19081

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Letters

A combined transmission spectrum of the Earth-sized exoplanets TRAPPIST-1 b and c p.69

Recently, temperate Earth-sized planets were discovered around the nearby star TRAPPIST-1; now, preliminary transmission spectra observations of the two inner planets by the Hubble Space Telescope suggest that these planets do not have a hydrogen-dominated atmosphere and are thus terrestrial, their atmospheric type still to be determined.

Julien de Wit, Hannah R. Wakeford, Michaël Gillon, Nikole K. Lewis, Jeff A. Valenti, Brice-Olivier Demory, Adam J. Burgasser, Artem Burdanov, Laetitia Delrez, Emmanuël Jehin + et al.

doi: 10.1038/nature18641

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Aggregate dust particles at comet 67P/Churyumov–Gerasimenko p.73

In situ measurements of dust particles at comet 67P/Churyumov–Gerasimenko confirm that the particles are aggregates of smaller, elongated grains even at the smallest sizes examined.

Mark S. Bentley, Roland Schmied, Thurid Mannel, Klaus Torkar, Harald Jeszenszky, Jens Romstedt, Anny-Chantal Levasseur-Regourd, Iris Weber, Elmar K. Jessberger, Pascale Ehrenfreund + et al.

doi: 10.1038/nature19091

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Dynamically encircling an exceptional point for asymmetric mode switching p.76

A two-mode waveguide is designed to realize a dynamical encircling of an exceptional point at which two resonances coincide in their frequency and their rate of decay; as a result the waveguide transmits only into a unique mode at either one of its two output ports.

Jörg Doppler, Alexei A. Mailybaev, Julian Böhm, Ulrich Kuhl, Adrian Girschik, Florian Libisch, Thomas J. Milburn, Peter Rabl, Nimrod Moiseyev & Stefan Rotter

doi: 10.1038/nature18605

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Ablation-cooled material removal with ultrafast bursts of pulses p.84

Ablation cooling is demonstrated as an effective means of removing material using successive bursts of laser pulses with short intraburst delay times; the technique allows the overall pulse energy to be decreased, overcoming negative thermal effects during the ablation process.

Can Kerse, Hamit Kalaycıoğlu, Parviz Elahi, Barbaros Çetin, Denizhan K. Kesim, Önder Akçaalan, Seydi Yavaş, Mehmet D. Aşık, Bülent Öktem, Heinar Hoogland + et al.

doi: 10.1038/nature18619

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Addition of multiple limiting resources reduces grassland diversity p.93

Analysis of multi-year nutrient enrichment experiments carried out on 45 global grassland sites show that an addition of an increasing number of nutrients leads to a reduction in plant species diversity, and competition for multiple below-ground resources promotes plant species diversity.

W. Stanley Harpole, Lauren L. Sullivan, Eric M. Lind, Jennifer Firn, Peter B. Adler, Elizabeth T. Borer, Jonathan Chase, Philip A. Fay, Yann Hautier, Helmut Hillebrand + et al.

doi: 10.1038/nature19324

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Serotonin engages an anxiety and fear-promoting circuit in the extended amygdala p.97

A brain circuit is identified through which serotonin induces an anxiety-like state; this circuit also mediates the anxiety-like behaviour induced by acute administration of the selective serotonin reuptake inhibitor fluoxetine and may underlie the early adverse events that some patients with anxiety disorders have to these types of drugs.

Catherine A. Marcinkiewcz, Christopher M. Mazzone, Giuseppe D’Agostino, Lindsay R. Halladay, J. Andrew Hardaway, Jeffrey F. DiBerto, Montserrat Navarro, Nathan Burnham, Claudia Cristiano, Cayce E. Dorrier + et al.

doi: 10.1038/nature19318

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HER2 expression identifies dynamic functional states within circulating breast cancer cells p.102

Patient-derived circulating tumour cells are used to characterize the dynamics and underlying plasticity of HER2 expression in non-HER2-amplified breast tumours.

Nicole Vincent Jordan, Aditya Bardia, Ben S. Wittner, Cyril Benes, Matteo Ligorio, Yu Zheng, Min Yu, Tilak K. Sundaresan, Joseph A. Licausi, Rushil Desai + et al.

doi: 10.1038/nature19328

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An endosomal tether undergoes an entropic collapse to bring vesicles together p.107

A new endosomal tethering mechanism involving a mechanochemical cycle of the dimeric coiled-coil protein EEA1 regulated by Rab5:GTP binding and GTP hydrolysis.

David H. Murray, Marcus Jahnel, Janelle Lauer, Mario J. Avellaneda, Nicolas Brouilly, Alice Cezanne, Hernán Morales-Navarrete, Enrico D. Perini, Charles Ferguson, Andrei N. Lupas + et al.

doi: 10.1038/nature19326

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Structural basis for inhibition of a voltage-gated Ca2+ channel by Ca2+ antagonist drugs p.117

Ca2+ antagonist drugs are widely used in therapy of cardiovascular disorders. Three chemical classes of drugs bind to three separate, but allosterically interacting, receptor sites on CaV1.2 channels, the most prominent voltage-gated Ca2+ (CaV) channel type in myocytes in cardiac and vascular smooth muscle. The 1,4-dihydropyridines are used primarily for treatment of hypertension and angina pectoris and are thought to act as allosteric modulators of voltage-dependent Ca2+ channel activation, whereas phenylalkylamines and benzothiazepines are used primarily for treatment of cardiac arrhythmias and are thought to physically block the pore. The structural basis for the different binding, action, and therapeutic uses of these drugs remains unknown. Here we present crystallographic and functional analyses of drug binding to the bacterial homotetrameric model CaV channel CaVAb, which is inhibited by dihydropyridines and phenylalkylamines with nanomolar affinity in a state-dependent manner. The binding site for amlodipine and other dihydropyridines is located on the external, lipid-facing surface of the pore module, positioned at the interface of two subunits. Dihydropyridine binding allosterically induces an asymmetric conformation of the selectivity filter, in which partially dehydrated Ca2+ interacts directly with one subunit and blocks the pore. In contrast, the phenylalkylamine Br-verapamil binds in the central cavity of the pore on the intracellular side of the selectivity filter, physically blocking the ion-conducting pathway. Structure-based mutations of key amino-acid residues confirm drug binding at both sites. Our results define the structural basis for binding of dihydropyridines and phenylalkylamines at their distinct receptor sites on CaV channels and offer key insights into their fundamental mechanisms of action and differential therapeutic uses in cardiovascular diseases.

Lin Tang, Tamer M. Gamal El-Din, Teresa M. Swanson, David C. Pryde, Todd Scheuer, Ning Zheng & William A. Catterall

doi: 10.1038/nature19102

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