Editorials
The EU’s fresh round of billion-euro Flagship research projects must be open to all types of science.
doi: 10.1038/540483a
Studies that inform policies on retirement need to assess occupations as well.
doi: 10.1038/540484b
But don’t fall for an old chestnut.
doi: 10.1038/540484a
News
Shift in focus comes in response to a changing world order and the threat of terrorism.
doi: 10.1038/540491a
Concerned by president-elect’s choice of advisers, researchers take steps to defend their fields.
doi: 10.1038/540492a
Third global fleet will soon be joined by Asian counterparts, setting the atmosphere abuzz with scientifically-useful radio-wave signals.
doi: 10.1038/nature.2016.21183
Programme aims to prevent crises similar to the recent Ebola epidemic.
doi: 10.1038/nature.2016.21134
Climate accords, controversial assisted reproduction and the CRISPR patent battle are among the year's top stories.
doi: 10.1038/540496a
Includes storms from space, southern stars and a striking cell.
doi: 10.1038/540500a
News Features
Ten people who mattered this year.
doi: 10.1038/540507a
News & Views
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
doi: 10.1038/nature21104
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
doi: 10.1038/540529a
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
doi: 10.1038/nature20489
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.
doi: 10.1038/nature21102
doi: 10.1038/nature21108
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
doi: 10.1038/540534a
Extracts from selected News & Views articles published this year.
doi: 10.1038/540536a
Articles
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
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.
doi: 10.1038/nature20796
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.
doi: 10.1038/nature20785
Letters
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.
doi: 10.1038/nature20614
Graph theory is used to guide the self-assembly of a complex consisting of 48 palladium ions and 96 ligands, with the topology of a tetravalent Goldberg polyhedron.
doi: 10.1038/nature20771
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.
doi: 10.1038/nature20139
The Agulhas Current has not intensified since the early 1990s, but has instead broadened as a result of more eddy activity.
doi: 10.1038/nature19853
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).
doi: 10.1038/nature20591
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.
doi: 10.1038/nature20602
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.
doi: 10.1038/nature20597
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.
doi: 10.1038/nature20609
Heat shock drives the expression of transcripts that bypass mRNA quality control for direct export and translation, allowing cells to survive extreme situations at the cost of accuracy.
doi: 10.1038/nature20572
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.
doi: 10.1038/nature20576
The authors report a 2.6 Å resolution crystal structure of the human CB1 cannabinoid receptor trapped in the inactive conformation and bound to the antagonist taranabant.
doi: 10.1038/nature20613
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.
doi: 10.1038/nature20561