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Nature's 10 p.315

Ten people who mattered this year.

Heidi Ledford, Davide Castelvecchi, Elie Dolgin, Sara Reardon, Elizabeth Gibney, Nicky Phillips & Alexandra Witze

doi: 10.1038/d41586-017-07763-y

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News & Views

Energy from thin air p.336

Advanced genomic-analysis techniques now suggest that microbial communities in cold, nutrient-poor Antarctic soils can acquire their energy from the oxidation of trace gases, rather than by photosynthesis.

doi: 10.1038/d41586-017-07579-w

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The origins of memory T cells p.337

Memory T cells protect against previously encountered pathogens, but their origins are unclear. Two studies track DNA modifications over time and find that these cells arise from effector T cells.

doi: 10.1038/d41586-017-08280-8

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Martian water stored underground p.339

Why did Mars lose so much of its surface water, whereas Earth retained its? Models of the evolution of minerals on the two planets suggest one explanation: the Martian water was drawn into the planetary interior.

doi: 10.1038/d41586-017-08670-y

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Tumour lymph vessels boost immunotherapy p.340

A high level of expression of the growth-factor protein VEGF-C is associated with tumours that have extensive lymph vessels and poor prognosis. It emerges that such tumours are highly susceptible to immunotherapy.

doi: 10.1038/d41586-017-08669-5

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Specks of insight into Alzheimer’s disease p.342

Inflammatory cues trigger microglial cells to release the protein ASC. It emerges that specks of ASC promote a hallmark of Alzheimer’s disease in the brains of mice — aggregation and deposition of amyloid-β protein.

doi: 10.1038/d41586-017-08668-6

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Articles

Microglia-derived ASC specks crossseed amyloid-β in Alzheimer’s disease p.355

The spreading of pathology within and between brain areas is a hallmark of neurodegenerative disorders. In patients with Alzheimer’s disease, deposition of amyloid-β is accompanied by activation of the innate immune system and involves inflammasome-dependent formation of ASC specks in microglia. ASC specks released by microglia bind rapidly to amyloid-β and increase the formation of amyloid-β oligomers and aggregates, acting as an inflammation-driven cross-seed for amyloid-β pathology. Here we show that intrahippocampal injection of ASC specks resulted in spreading of amyloid-β pathology in transgenic double-mutant APPSwePSEN1dE9 mice. By contrast, homogenates from brains of APPSwePSEN1dE9 mice failed to induce seeding and spreading of amyloid-β pathology in ASC-deficient APPSwePSEN1dE9 mice. Moreover, co-application of an anti-ASC antibody blocked the increase in amyloid-β pathology in APPSwePSEN1dE9 mice. These findings support the concept that inflammasome activation is connected to seeding and spreading of amyloid-β pathology in patients with Alzheimer’s disease.

Carmen Venegas, Sathish Kumar, Bernardo S. Franklin, Tobias Dierkes, Rebecca Brinkschulte, Dario Tejera, Ana Vieira-Saecker, Stephanie Schwartz, Francesco Santarelli, Markus P. Kummer + et al.

doi: 10.1038/nature25158

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Origin and differentiation of human memory CD8 T cells after vaccination p.362

In vivo deuterium labelling reveals a quiescent population of long-lived human virus-specific memory CD8 T cells that maintain the epigenetic landscape of effector cells, which facilitates rapid responses to pathogen re-exposure.

Rama S. Akondy, Mark Fitch, Srilatha Edupuganti, Shu Yang, Haydn T. Kissick, Kelvin W. Li, Ben A. Youngblood, Hossam A. Abdelsamed, Donald J. McGuire, Kristen W. Cohen + et al.

doi: 10.1038/nature24633

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Mechanisms of mTORC1 activation by RHEB and inhibition by PRAS40 p.368

The cryo-electron microscopy and crystal structures of several mTORC1 complexes, and accompanying biochemical analyses, shed light on how mTORC1 is regulated and how cancer mutations lead to its hyperactivation.

Haijuan Yang, Xiaolu Jiang, Buren Li, Hyo J. Yang, Meredith Miller, Angela Yang, Ankita Dhar & Nikola P. Pavletich

doi: 10.1038/nature25023

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Letters

Blazar spectral variability as explained by a twisted inhomogeneous jet p.374

The spectral variability of the blazar CTA 102 during a recent extreme outburst could be explained by a twisted, inhomogeneous jet containing regions of different orientations that vary in time.

C. M. Raiteri, M. Villata, J. A. Acosta-Pulido, I. Agudo, A. A. Arkharov, R. Bachev, G. V. Baida, E. Benítez, G. A. Borman, W. Boschin + et al.

doi: 10.1038/nature24623

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Discovery of a big void in Khufu’s Pyramid by observation of cosmic-ray muons p.386

Cosmic-ray muon radiography has been used to non-invasively visualize the voids in the Great Pyramid (Khufu’s Pyramid), revealing a large void situated above the Grand Gallery.

Kunihiro Morishima, Mitsuaki Kuno, Akira Nishio, Nobuko Kitagawa, Yuta Manabe, Masaki Moto, Fumihiko Takasaki, Hirofumi Fujii, Kotaro Satoh, Hideyo Kodama + et al.

doi: 10.1038/nature24647

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Synchrotron scanning reveals amphibious ecomorphology in a new clade of bird-like dinosaurs p.395

The recently discovered theropod Halszkaraptor escuillei reveals a novel basal dromaeosaurid clade, and its adaptations that suggest a semi-aquatic predatory lifestyle add an additional ecomorphology to those developed by non-avian maniraptorans.

Andrea Cau, Vincent Beyrand, Dennis F. A. E. Voeten, Vincent Fernandez, Paul Tafforeau, Koen Stein, Rinchen Barsbold, Khishigjav Tsogtbaatar, Philip J. Currie & Pascal Godefroit

doi: 10.1038/nature24679

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Atmospheric trace gases support primary production in Antarctic desert surface soil p.400

Metagenomic and biochemical analyses of soil samples from Antarctic desert regions provides evidence that bacteria in these soils derive carbon and energy from atmospheric CO, H2 and CO2.

Mukan Ji, Chris Greening, Inka Vanwonterghem, Carlo R. Carere, Sean K. Bay, Jason A. Steen, Kate Montgomery, Thomas Lines, John Beardall, Josie van Dorst + et al.

doi: 10.1038/nature25014

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Effector CD8 T cells dedifferentiate into long-lived memory cells p.404

DNA methylation profiling of virus-specific T cells during acute viral infection in mice provides evidence that a fate-permissive subset of effector CD8 T cells dedifferentiates into long-lived memory T cells.

Ben Youngblood, J. Scott Hale, Haydn T. Kissick, Eunseon Ahn, Xiaojin Xu, Andreas Wieland, Koichi Araki, Erin E. West, Hazem E. Ghoneim, Yiping Fan + et al.

doi: 10.1038/nature25144

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Dynamics of phosphoinositide conversion in clathrin-mediated endocytic traffic p.410

‘Coincidence-detecting’ phosphoinositide sensors are used to study changes in the phosphoinositide lipid species found in membranes during the development and maturation of endocytic clathrin-coated vesicles.

Kangmin He, Robert Marsland III, Srigokul Upadhyayula, Eli Song, Song Dang, Benjamin R. Capraro, Weiming Wang, Wesley Skillern, Raphael Gaudin, Minghe Ma + et al.

doi: 10.1038/nature25146

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Evolution of a designed protein assembly encapsulating its own RNA genome p.415

Computationally designed icosahedral protein-based assemblies can protect their genetic material and evolve in biochemical environments, suggesting a route to the custom design of synthetic nanomaterials for non-viral drug delivery.

Gabriel L. Butterfield, Marc J. Lajoie, Heather H. Gustafson, Drew L. Sellers, Una Nattermann, Daniel Ellis, Jacob B. Bale, Sharon Ke, Garreck H. Lenz, Angelica Yehdego + et al.

doi: 10.1038/nature25157

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Cryo-EM structures of the TMEM16A calcium-activated chloride channel p.426

Calcium-activated chloride channels (CaCCs) encoded by TMEM16A control neuronal signalling, smooth muscle contraction, airway and exocrine gland secretion, and rhythmic movements of the gastrointestinal system. To understand how CaCCs mediate and control anion permeation to fulfil these physiological functions, knowledge of the mammalian TMEM16A structure and identification of its pore-lining residues are essential. TMEM16A forms a dimer with two pores. Previous CaCC structural analyses have relied on homology modelling of a homologue (nhTMEM16) from the fungus Nectria haematococca that functions primarily as a lipid scramblase, as well as subnanometre-resolution electron cryo-microscopy. Here we present de novo atomic structures of the transmembrane domains of mouse TMEM16A in nanodiscs and in lauryl maltose neopentyl glycol as determined by single-particle electron cryo-microscopy. These structures reveal the ion permeation pore and represent different functional states. The structure in lauryl maltose neopentyl glycol has one Ca2+ ion resolved within each monomer with a constricted pore; this is likely to correspond to a closed state, because a CaCC with a single Ca2+ occupancy requires membrane depolarization in order to open (C.J.P. et al., manuscript submitted). The structure in nanodiscs has two Ca2+ ions per monomer and its pore is in a closed conformation; this probably reflects channel rundown, which is the gradual loss of channel activity that follows prolonged CaCC activation in 1 mM Ca2+. Our mutagenesis and electrophysiological studies, prompted by analyses of the structures, identified ten residues distributed along the pore that interact with permeant anions and affect anion selectivity, as well as seven pore-lining residues that cluster near pore constrictions and regulate channel gating. Together, these results clarify the basis of CaCC anion conduction.

Shangyu Dang, Shengjie Feng, Jason Tien, Christian J. Peters, David Bulkley, Marco Lolicato, Jianhua Zhao, Kathrin Zuberbühler, Wenlei Ye, Lijun Qi + et al.

doi: 10.1038/nature25024

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