Volume 539 Issue 7627



News Features

News & Views

Stones that could cause ripples p.34

Monkeys have been observed pounding stones and unintentionally forming sharp-edged, tool-like fragments. This deliberate breakage raises questions about the evolution of intentional stone modification. See Letter p.85

doi: 10.1038/nature19484

Telomere-lengthening mechanism revealed p.35

Shortening of the ends of chromosomes limits a cell's lifespan. Some cancer cells avoid this fate through a mechanism called alternative lengthening of telomeres, molecular details of which have now been defined. See Article p.54

doi: 10.1038/nature19483

Turbulence in a quantum gas p.36

The discovery of a cascade of sound waves across many wavelengths in an ultracold atomic gas advances our understanding of turbulence in fluids governed by quantum mechanics. See Letter p.72

doi: 10.1038/539036a

Phosphate on, rubbish out p.38

A previously unknown way in which cells mark proteins for destruction has been found in bacteria — phosphorylation of the amino acid arginine targets proteins for degradation by protease enzymes. See Article p.48

doi: 10.1038/539038a

Sound and meaning in the world's languages p.39

The sounds of words that represent particular meanings are usually thought to vary arbitrarily across languages. However, a large-scale study of languages finds that some associations between sound and meaning are widespread.

doi: 10.1038/nature20474

Axions exposed p.40

Physicists are hunting for a particle called the axion that could solve two major puzzles in fundamental physics. An ambitious study calculates the expected mass of this particle, which might reshape the experimental searches. See Letter p.69

doi: 10.1038/539040a



Wild monkeys flake stone tools p.85

Wild capuchin monkeys in Brazil deliberately break stones, unintentionally producing flakes similar to the ancient sharp-edged flakes characterized as intentionally produced Pliocene–Pleistocene hominin tools, although why they do so remains unclear.

doi: 10.1038/nature20112

Olfactory receptor pseudo-pseudogenes p.93

Drosophila sechellia, a species closely related to the model species Drosophila melanogaster, bypasses a premature stop codon in neuronal cells to express a functional olfactory receptor protein from an assumed pseudogene template.

doi: 10.1038/nature19824

Single-cell RNA-seq identifies a PD-1hi ILC progenitor and defines its development pathway p.102

Innate lymphoid cells (ILCs) functionally resemble T lymphocytes in cytotoxicity and cytokine production but lack antigen-specific receptors, and they are important regulators of immune responses and tissue homeostasis. ILCs are generated from common lymphoid progenitors, which are subsequently committed to innate lymphoid lineages in the α-lymphoid progenitor, early innate lymphoid progenitor, common helper innate lymphoid progenitor and innate lymphoid cell progenitor compartments. ILCs consist of conventional natural killer cells and helper-like cells (ILC1, ILC2 and ILC3). Despite recent advances, the cellular heterogeneity, developmental trajectory and signalling dependence of ILC progenitors are not fully understood. Here, using single-cell RNA-sequencing (scRNA-seq) of mouse bone marrow progenitors, we reveal ILC precursor subsets, delineate distinct ILC development stages and pathways, and report that high expression of programmed death 1 (PD-1hi) marked a committed ILC progenitor that was essentially identical to an innate lymphoid cell progenitor. Our data defined PD-1hiIL-25Rhi as an early checkpoint in ILC2 development, which was abolished by deficiency in the zinc-finger protein Bcl11b but restored by IL-25R overexpression. Similar to T lymphocytes, PD-1 was upregulated on activated ILCs. Administration of a PD-1 antibody depleted PD-1hi ILCs and reduced cytokine levels in an influenza infection model in mice, and blocked papain-induced acute lung inflammation. These results provide a perspective for exploring PD-1 and its ligand (PD-L1) in immunotherapy, and allow effective manipulation of the immune system for disease prevention and therapy.

doi: 10.1038/nature20105

On-target efficacy of a HIF-2α antagonist in preclinical kidney cancer models p.107

Clear cell renal cell carcinoma, the most common form of kidney cancer, is usually linked to inactivation of the pVHL tumour suppressor protein and consequent accumulation of the HIF-2α transcription factor (also known as EPAS1). Here we show that a small molecule (PT2399) that directly inhibits HIF-2α causes tumour regression in preclinical mouse models of primary and metastatic pVHL-defective clear cell renal cell carcinoma in an on-target fashion. pVHL-defective clear cell renal cell carcinoma cell lines display unexpectedly variable sensitivity to PT2399, however, suggesting the need for predictive biomarkers to be developed to use this approach optimally in the clinic.

doi: 10.1038/nature19795