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Pathways of parallel progression p.528

Two studies in mice identify mechanisms by which tumour cells disseminate in very early breast cancer. Both show that these cells colonize distant tissues more efficiently than their later counterparts. See Article p.552 & Letter p.588

Cyrus M. Ghajar & Mina J. Bissell

doi: 10.1038/nature21104


Unexplored territory for self-assembly p.529

Cage-like structures can self-assemble from suitable metal ions and organic linkers, but the size of the assemblies was limited. The surprise discovery of a new series of cages opens up fresh horizons for self-assembly. See Letter p.563

Florian Beuerle

doi: 10.1038/540529a


A turbulent path to plaque formation p.531

Plaque deposits often occur in curved arterial regions with turbulent blood flow. Endothelial cells have been found to respond to blood flow through a previously unidentified signalling pathway that affects plaque build-up. See Letter p.579

Vedanta Mehta & Ellie Mehta

doi: 10.1038/nature20489


Sharks shift their spine into high gear p.532

It emerges that a dogfish shark's spine becomes stiffer as the fish swims faster, enabling the animal to swim efficiently at different speeds. The finding could also provide inspiration for the design of robotic biomaterials.

Matthew A. Kolmann & Adam P. Summers

doi: 10.1038/nature21102


Quantum mechanics in a spin p.534

Quantum spin liquids are exotic states of matter first predicted more than 40 years ago. An inorganic material has properties consistent with these predictions, revealing details about the nature of quantum matter. See Letter p.559

Leon Balents

doi: 10.1038/540534a



Redefining the invertebrate RNA virosphere p.539

Profiling the total RNA of 220 invertebrate species leads to the discovery of almost 1,500 new species of RNA virus, revealing that the RNA virosphere is much more diverse than was previously thought.

doi: 10.1038/nature20167

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Persistent microbiome alterations modulate the rate of post-dieting weight regain p.544

The identification of an intestinal microbiome signature that persists after successful dieting in obese mice and contributes to faster weight regain upon re-exposure to an obesity-promoting diet, and that transmits the altered weight regain phenotype to non-dieting mice.

Christoph A. Thaiss, Shlomik Itav, Daphna Rothschild, Mariska T. Meijer, Maayan Levy, Claudia Moresi, Lenka Dohnalová, Sofia Braverman, Shachar Rozin, Sergey Malitsky + et al.

doi: 10.1038/nature20796

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Early dissemination seeds metastasis in breast cancer p.552

Two related papers show that cells disseminated from malignant lesions at early time points during tumorigenesis can contribute to metastases at distant organs and provide insights into the molecular basis of dissemination.

Hedayatollah Hosseini, Milan M. S. Obradović, Martin Hoffmann, Kathryn L. Harper, Maria Soledad Sosa, Melanie Werner-Klein, Lahiri Kanth Nanduri, Christian Werno, Carolin Ehrl, Matthias Maneck + et al.

doi: 10.1038/nature20785

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Evidence for a spinon Fermi surface in a triangular-lattice quantum-spin-liquid candidate p.559

A spin excitation continuum across a large region of the Brillouin zone that persists at near-zero temperatures provides evidence for a quantum spin liquid state with a spinon Fermi surface in YbMgGaO4.

Yao Shen, Yao-Dong Li, Hongliang Wo, Yuesheng Li, Shoudong Shen, Bingying Pan, Qisi Wang, H. C. Walker, P. Steffens, M. Boehm + et al.

doi: 10.1038/nature20614

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Water balance creates a threshold in soil pH at the global scale p.567

There is an abrupt transition from alkaline to acid soil pH when mean annual precipitation exceeds mean annual potential evapotranspiration, demonstrating that climate creates a nonlinear pattern in soil solution chemistry at the global scale.

E. W. Slessarev, Y. Lin, N. L. Bingham, J. E. Johnson, Y. Dai, J. P. Schimel & O. A. Chadwick

doi: 10.1038/nature20139

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Chemical intervention in plant sugar signalling increases yield and resilience p.574

Treatment with signalling precursors of trehalose-6-phosphate allows light-triggered release of trehalose-6-phosphate in Arabidopsis thaliana and increases the yield and drought resistance of spring wheat (Triticum aestivum).

Cara A. Griffiths, Ram Sagar, Yiqun Geng, Lucia F. Primavesi, Mitul K. Patel, Melissa K. Passarelli, Ian S. Gilmore, Rory T. Steven, Josephine Bunch, Matthew J. Paul + et al.

doi: 10.1038/nature20591

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Integrin-YAP/TAZ-JNK cascade mediates atheroprotective effect of unidirectional shear flow p.579

The Yorkie homologues YAP (Yes-associated protein) and TAZ (transcriptional coactivator with PDZ-binding motif, also known as WWTR1), effectors of the Hippo pathway, have been identified as mediators for mechanical stimuli. However, the role of YAP/TAZ in haemodynamics-induced mechanotransduction and pathogenesis of atherosclerosis remains unclear. Here we show that endothelial YAP/TAZ activity is regulated by different patterns of blood flow, and YAP/TAZ inhibition suppresses inflammation and retards atherogenesis. Atheroprone-disturbed flow increases whereas atheroprotective unidirectional shear stress inhibits YAP/TAZ activity. Unidirectional shear stress activates integrin and promotes integrin–Gα13 interaction, leading to RhoA inhibition and YAP phosphorylation and suppression. YAP/TAZ inhibition suppresses JNK signalling and downregulates pro-inflammatory genes expression, thereby reducing monocyte attachment and infiltration. In vivo endothelial-specific YAP overexpression exacerbates, while CRISPR/Cas9-mediated Yap knockdown in endothelium retards, plaque formation in ApoE/ mice. We also show several existing anti-atherosclerotic agents such as statins inhibit YAP/TAZ transactivation. On the other hand, simvastatin fails to suppress constitutively active YAP/TAZ-induced pro-inflammatory gene expression in endothelial cells, indicating that YAP/TAZ inhibition could contribute to the anti-inflammatory effect of simvastatin. Furthermore, activation of integrin by oral administration of MnCl2 reduces plaque formation. Taken together, our results indicate that integrin–Gα13–RhoA–YAP pathway holds promise as a novel drug target against atherosclerosis.

Li Wang, Jiang-Yun Luo, Bochuan Li, Xiao Yu Tian, Li-Jing Chen, Yuhong Huang, Jian Liu, Dan Deng, Chi Wai Lau, Song Wan + et al.

doi: 10.1038/nature20602

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NLRC3 is an inhibitory sensor of PI3K–mTOR pathways in cancer p.583

Mice deficient in the protein NLRC3 are highly prone to colitis and tumour development in the colon as NLRC3 suppresses the activation of mTOR signalling pathways that help drive tumorigenesis.

Rajendra Karki, Si Ming Man, R. K. Subbarao Malireddi, Sannula Kesavardhana, Qifan Zhu, Amanda R. Burton, Bhesh Raj Sharma, Xiaopeng Qi, Stephane Pelletier, Peter Vogel + et al.

doi: 10.1038/nature20597

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Mechanism of early dissemination and metastasis in Her2+ mammary cancer p.588

Metastasis is the leading cause of cancer-related deaths; metastatic lesions develop from disseminated cancer cells (DCCs) that can remain dormant. Metastasis-initiating cells are thought to originate from a subpopulation present in progressed, invasive tumours. However, DCCs detected in patients before the manifestation of breast-cancer metastasis contain fewer genetic abnormalities than primary tumours or than DCCs from patients with metastases. These findings, and those in pancreatic cancer and melanoma models, indicate that dissemination might occur during the early stages of tumour evolution. However, the mechanisms that might allow early disseminated cancer cells (eDCCs) to complete all steps of metastasis are unknown. Here we show that, in early lesions in mice and before any apparent primary tumour masses are detected, there is a sub-population of Her2+p-p38lop-Atf2loTwist1hiE-cadlo early cancer cells that is invasive and can spread to target organs. Intra-vital imaging and organoid studies of early lesions showed that Her2+ eDCC precursors invaded locally, intravasated and lodged in target organs. Her2+ eDCCs activated a Wnt-dependent epithelial–mesenchymal transition (EMT)-like dissemination program but without complete loss of the epithelial phenotype, which was reversed by Her2 or Wnt inhibition. Notably, although the majority of eDCCs were Twist1hiE-cadlo and dormant, they eventually initiated metastasis. Our work identifies a mechanism for early dissemination in which Her2 aberrantly activates a program similar to mammary ductal branching that generates eDCCs that are capable of forming metastasis after a dormancy phase.

Kathryn L. Harper, Maria Soledad Sosa, David Entenberg, Hedayatollah Hosseini, Julie F. Cheung, Rita Nobre, Alvaro Avivar-Valderas, Chandandaneep Nagi, Nomeda Girnius, Roger J. Davis + et al.

doi: 10.1038/nature20609

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Near-atomic-resolution cryo-EM analysis of the Salmonella T3S injectisome basal body p.597

The authors report the structure of the assembled membrane spanning ring forming proteins of the Salmonella Typhimurium injectisome basal body, including the first atomic structure of a member of the secretin family of outer-membrane pores.

L. J. Worrall, C. Hong, M. Vuckovic, W. Deng, J. R. C. Bergeron, D. D Majewski, R. K. Huang, T. Spreter, B. B. Finlay, Z. Yu + et al.

doi: 10.1038/nature20576

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Structure of RNA polymerase I transcribing ribosomal DNA genes p.607

Structures of budding yeast RNA polymerase I in a catalytically active conformation are presented and confirmed by visualizing processive transcription along ribosomal DNA genes; they support a general model for transcription elongation in which contracted and expanded polymerase conformations are associated with active and inactive states, respectively.

Simon Neyer, Michael Kunz, Christian Geiss, Merle Hantsche, Victor-Valentin Hodirnau, Anja Seybert, Christoph Engel, Margot P. Scheffer, Patrick Cramer & Achilleas S. Frangakis

doi: 10.1038/nature20561

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