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Of rats and resilience p.32

A revised timeline for the arrival of settlers on Mangaia island in Polynesia reveals the resilience of this population, which overcame an environmental crisis through bold measures to support a sustainable society.

Jared Diamond

doi: 10.1038/545032a

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Role of repeats in protein clearance p.33

Mutant proteins that contain stretches called polyQ repeats can misfold or form aggregates linked to neurodegeneration. It emerges that some polyQ-containing proteins regulate a process that degrades misfolded proteins. See Letter p.108

Dale D. O. Martin & Michael R. Hayden

doi: 10.1038/nature22489

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Nickel steps towards selectivity p.35

Hydrocarbons called alkenes are isolated from petroleum as mixtures of isomers, often making it hard to use them as reagents for synthesis. A reaction involving a migrating nickel atom offers a possible solution. See Letter p.84

Matthew Gaunt & Patrick Williamson

doi: 10.1038/545035a

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Chaperone protein gets personal p.36

Two studies of the molecular chaperone protein HSP90 reveal how complex traits can be shaped by genetic and environmental context. This work highlights the challenges of personalized medicine.

Mark L. Siegal

doi: 10.1038/nature22487

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The 'pause' unpacked p.37

Short-term climate trends are sensitive to definitions, data and testing. This sensitivity underlies an alleged pause in global warming, and highlights the need for meaningful definitions to sustain claims that it was real. See Analysis p.41

James S. Risbey & Stephan Lewandowsky

doi: 10.1038/545037a

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Advances in mini-brain technology p.39

Two studies integrate cutting-edge techniques to grow and analyse 3D cultured tissues that resemble human brain structures, enabling examination of how brain regions interact and neurons mature. See Articles p.48 & p.54

J. Gray Camp & Barbara Treutlein

doi: 10.1038/545039a

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Analysis

Reconciling controversies about the ‘global warming hiatus’ p.41

Apparently contradictory conclusions regarding the ‘global warming hiatus’ are reconciled, strengthening the current scientific understanding that long-term global warming is extremely likely to be of anthropogenic origin.

Iselin Medhaug, Martin B. Stolpe, Erich M. Fischer & Reto Knutti

doi: 10.1038/nature22315

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Articles

Cell diversity and network dynamics in photosensitive human brain organoids p.48

Apparently contradictory conclusions regarding the ‘global warming hiatus’ are reconciled, strengthening the current scientific understanding that long-term global warming is extremely likely to be of anthropogenic origin.

Giorgia Quadrato, Tuan Nguyen, Evan Z. Macosko, John L. Sherwood, Sung Min Yang, Daniel R. Berger, Natalie Maria, Jorg Scholvin, Melissa Goldman, Justin P. Kinney + et al.

doi: 10.1038/nature22047

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Assembly of functionally integrated human forebrain spheroids p.54

Human pluripotent stem cells were used to develop dorsal and ventral forebrain 3D spheroids, which can be assembled to study interneuron migration and to derive a functionally integrated forebrain system with cortical interneurons and glutamatergic neurons.

Fikri Birey, Jimena Andersen, Christopher D. Makinson, Saiful Islam, Wu Wei, Nina Huber, H. Christina Fan, Kimberly R. Cordes Metzler, Georgia Panagiotakos, Nicholas Thom + et al.

doi: 10.1038/nature22330

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T-cell invigoration to tumour burden ratio associated with anti-PD-1 response p.60

The clinical benefit of anti-PD-1 antibody treatment is dependent on the extent to which exhausted CD8 T cells are reinvigorated in relation to the tumour burden of the patient.

Alexander C. Huang, Michael A. Postow, Robert J. Orlowski, Rosemarie Mick, Bertram Bengsch, Sasikanth Manne, Wei Xu, Shannon Harmon, Josephine R. Giles, Brandon Wenz + et al.

doi: 10.1038/nature22079

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Letters

Observation of the frozen charge of a Kondo resonance p.71

In a quantum dot in the Kondo regime, electrical charges are effectively frozen, but the quantum dot remains electrically conducting owing to strong electron–electron correlations.

M. M. Desjardins, J. J. Viennot, M. C. Dartiailh, L. E. Bruhat, M. R. Delbecq, M. Lee, M.-S. Choi, A. Cottet & T. Kontos

doi: 10.1038/nature21704

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Observed quantization of anyonic heat flow p.75

Quasiparticles in strongly interacting fractional quantum Hall systems carry heat according to the same quantization of thermal conductance as for particles in non-interacting systems.

Mitali Banerjee, Moty Heiblum, Amir Rosenblatt, Yuval Oreg, Dima E. Feldman, Ady Stern & Vladimir Umansky

doi: 10.1038/nature22052

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Dual-phase nanostructuring as a route to high-strength magnesium alloys p.80

Combining the benefits of nanocrystals with those of amorphous metallic glasses leads to a dual-phase material—comprising sub-10-nanometre-sized nanocrystalline grains embedded in amorphous glassy shells—that exhibits a strength approaching the ideal theoretical limit.

Ge Wu, Ka-Cheung Chan, Linli Zhu, Ligang Sun & Jian Lu

doi: 10.1038/nature21691

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Burgess Shale fossils illustrate the origin of the mandibulate body plan p.89

Tokummia katalepsis from the Burgess Shale had a pair of mandibles and maxilliped claws, showing that large bivalved arthropods from the Cambrian period are forerunners of myriapods and pancrustaceans, thereby providing a basis for the origin of the hyperdiverse mandibulate body plan.

Cédric Aria & Jean-Bernard Caron

doi: 10.1038/nature22080

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The mitochondrial Na+/Ca2+ exchanger is essential for Ca2+ homeostasis and viability p.93

Conditional deletion of the mitochondrial Na+/Ca2+ exchanger NCLX in adult mouse hearts causes sudden death due to mitochondrial calcium overload, whereas its overexpression limits cell death elicited by ischaemia reperfusion injury and heart failure.

Timothy S. Luongo, Jonathan P. Lambert, Polina Gross, Mary Nwokedi, Alyssa A. Lombardi, Santhanam Shanmughapriya, April C. Carpenter, Devin Kolmetzky, Erhe Gao, Jop H. van Berlo + et al.

doi: 10.1038/nature22082

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Tumour ischaemia by interferon-γ resembles physiological blood vessel regression p.98

The relative contribution of the effector molecules produced by T cells to tumour rejection is unclear, but interferon-γ (IFNγ) is critical in most of the analysed models. Although IFNγ can impede tumour growth by acting directly on cancer cells, it must also act on the tumour stroma for effective rejection of large, established tumours. However, which stroma cells respond to IFNγ and by which mechanism IFNγ contributes to tumour rejection through stromal targeting have remained unknown. Here we use a model of IFNγ induction and an IFNγ–GFP fusion protein in large, vascularized tumours growing in mice that express the IFNγ receptor exclusively in defined cell types. Responsiveness to IFNγ by myeloid cells and other haematopoietic cells, including T cells or fibroblasts, was not sufficient for IFNγ-induced tumour regression, whereas responsiveness of endothelial cells to IFNγ was necessary and sufficient. Intravital microscopy revealed IFNγ-induced regression of the tumour vasculature, resulting in arrest of blood flow and subsequent collapse of tumours, similar to non-haemorrhagic necrosis in ischaemia and unlike haemorrhagic necrosis induced by tumour necrosis factor. The early events of IFNγ-induced tumour ischaemia resemble non-apoptotic blood vessel regression during development, wound healing or IFNγ-mediated, pregnancy-induced remodelling of uterine arteries. A better mechanistic understanding of how solid tumours are rejected may aid the design of more effective protocols for adoptive T-cell therapy.

Thomas Kammertoens, Christian Friese, Ainhoa Arina, Christian Idel, Dana Briesemeister, Michael Rothe, Andranik Ivanov, Anna Szymborska, Giannino Patone, Severine Kunz + et al.

doi: 10.1038/nature22311

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Transmission of cytokinesis forces via E-cadherin dilution and actomyosin flows p.103

Under physiological forces, resulting from cytokinesis, the mechanosensitivity of adherens junction arises from a local decrease in E-cadherin concentration and results in actomyosin flows.

Diana Pinheiro, Edouard Hannezo, Sophie Herszterg, Floris Bosveld, Isabelle Gaugue, Maria Balakireva, Zhimin Wang, Inês Cristo, Stéphane U. Rigaud, Olga Markova + et al.

doi: 10.1038/nature22041

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Polyglutamine tracts regulate beclin 1-dependent autophagy p.108

The polyglutamine domain in ataxin 3, which is expanded in spinocerebellar ataxia type 3, allows normal ataxin 3 to interact with and deubiquitinate beclin 1 and thereby to promote autophagy.

Avraham Ashkenazi, Carla F. Bento, Thomas Ricketts, Mariella Vicinanza, Farah Siddiqi, Mariana Pavel, Ferdinando Squitieri, Maarten C. Hardenberg, Sara Imarisio, Fiona M. Menzies + et al.

doi: 10.1038/nature22078

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Structural insight into allosteric modulation of protease-activated receptor 2 p.112

Crystal structures of protease-activated receptor 2 (PAR2) in complex with two different antagonist ligands and with a blocking antibody reveal binding sites that are distinct from those found on PAR1, offering new leads for structure-based drug design.

Robert K. Y. Cheng, Cédric Fiez-Vandal, Oliver Schlenker, Karl Edman, Birte Aggeler, Dean G. Brown, Giles A. Brown, Robert M. Cooke, Christoph E. Dumelin, Andrew S. Doré + et al.

doi: 10.1038/nature22309

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