Volume 539 Number 7629



Reality must trump rhetoric after US election shock p.329

It is time for scientists and politicians alike to constructively engage with core issues — from climate change and energy independence to social inequality.

doi: 10.1038/539329a


Being able to explain your work to passers-by is laudable — but not always possible p.330

The first person to invoke the ‘man on the street’ has been identified, but sometimes maths is just too difficult to make simple.

doi: 10.1038/539330a


Fed up of Earth? Try Mars p.330

Establishing a Martian outpost is likely to bring many of the same societal problems we face on Earth.

doi: 10.1038/539330b



The ultimate experiment: How Trump will handle science p.337

Climate-change and immigration policies raise alarm, but much of the incoming US president's agenda is simply unknown.

doi: 10.1038/nature.2016.20971


Pollsters struggle to explain failures of US presidential forecasts p.339

Most surveys did not predict Donald Trump’s victory over Hillary Clinton.

doi: 10.1038/nature.2016.20968


Disgraced stem-cell entrepreneur under fresh investigation p.340

Davide Vannoni is barred from offering a controversial stem-cell therapy in Italy but may be continuing his work abroad.

doi: 10.1038/539340a


I can haz more science emoji? Host of nerd icons proposed p.341

At a conference in San Francisco, a group drafted proposals to add more planets, instruments and other science icons to the keyboard.

doi: 10.1038/nature.2016.20960


Rwanda feels the pinch as donors slash health aid p.342

Country's progress on public health and science prompts funding shift to more-troubled nations.

doi: 10.1038/539342a


Open peer review finds more takers p.343

Journal experiments and surveys suggest scientists are coming round to the idea of publishing review reports.

doi: 10.1038/nature.2016.20969

News Features


How much longer can Antarctica’s hostile ocean delay global warming? p.346


doi: 10.1038/539346a

News & Views


Optical physics: Clear directions for random lasers p.360


doi: 10.1038/nature20477


Molecular biology: Mature proteins braced by a chaperone p.361


doi: 10.1038/nature20470


Geochemistry: Ions surprise in Earth's deep fluids p.362


doi: 10.1038/539362a


Neuroscience: Sleepy and dreamless mutant mice p.364


doi: 10.1038/nature20471


Materials science: Semiconductors that stretch and heal p.365


doi: 10.1038/539365a


Microbiology: Deep-sea secrets of butane metabolism p.367


doi: 10.1038/539367a



The effects of Δ9-tetrahydrocannabinol on the dopamine system p.369

A review into the complex effects of Δ9-tetrahydrocannabinol on the dopamine system, examining data from animal and human studies and discussing the necessary future direction of research.

doi: 10.1038/nature20153



Forward-genetics analysis of sleep in randomly mutagenized mice p.378

Two mutations affecting the sleep–wakefulness balance in mice are detected, showing that the SIK3 protein kinase is essential for determining daily wake time, and the NALCN cation channel regulates the duration of rapid eye movement sleep.

doi: 10.1038/nature20142


CRISPR/Cas9 β-globin gene targeting in human haematopoietic stem cells p.384

These preclinical studies outline a CRISPR-based methodology for correcting β-globin gene mutations in haematopoietic stem cells to advance the development of next-generation therapies for β-haemoglobinopathies.

doi: 10.1038/nature20134


LKB1 loss links serine metabolism to DNA methylation and tumorigenesis p.390

Human tumours with mutations in LKB1 and Kras have a specific hypermetabolic state associated with increased DNA methylation, pointing to potential metabolic and epigenetic vulnerabilities of specific tumours.

doi: 10.1038/nature20132


Thermophilic archaea activate butane via alkyl-coenzyme M formation p.396

Anaerobic archaea enriched in thermophilic microbial consortia completely degrade butane by modifying mechanisms which were hitherto thought to be specific to methane metabolism.

doi: 10.1038/nature20152



Tidal evolution of the Moon from a high-obliquity, high-angular-momentum Earth p.402

A model of the Moon’s tidal evolution, starting from the fast-spinning, high-obliquity Earth that would be expected after a giant impact, reveals that solar perturbations on the Moon’s orbit naturally produce the current lunar inclination and Earth’s low obliquity.

doi: 10.1038/nature19846


Nanoscale thermal imaging of dissipation in quantum systems p.407

A cryogenic thermal imaging technique that uses a superconducting quantum interference device fabricated on the tip of a sharp pipette can be used to image the thermal signature of extremely low power nanometre-scale dissipation processes.

doi: 10.1038/nature19843


Intrinsically stretchable and healable semiconducting polymer for organic transistors p.411

Introducing non-covalent crosslinking moieties to polymer semiconductors produces a stretchable and healable material suitable for wearable electronics.

doi: 10.1038/nature20102


Amazon boundary layer aerosol concentration sustained by vertical transport during rainfall p.416

Rapid vertical transport of small aerosol particles from the free troposphere to the atmospheric boundary layer occurs during precipitation and maintains the population of aerosol particles over Amazonia.

doi: 10.1038/nature19819


Implications for metal and volatile cycles from the pH of subduction zone fluids p.420

A thermodynamic model of fluid pH and its variability in Earth’s mantle and subducting crust highlights chemical feedbacks that connect deep Earth to surface processes.

doi: 10.1038/nature20103


Variability in plant nutrients reduces insect herbivore performance p.425

Variation in plant nutrient levels suppresses insect herbivore populations and the homogenous nutrient content of modern agricultural crops could be contributing to insect pest outbreaks.

doi: 10.1038/nature20140


Neuromodulators signal through astrocytes to alter neural circuit activity and behaviour p.428

Calcium signalling in astrocytes, driven through the octopamine/tyramine receptor and the TRP channel Water witch, is essential for neuromodulation and sensory responses in Drosophila larvae.

doi: 10.1038/nature20145


Transcription of the non-coding RNA upperhand controls Hand2 expression and heart development p.433

Transcription of a long non-coding RNA, known as upperhand (Uph) located upstream of the HAND2 transcription factor is required to maintain transcription of the Hand2 gene by RNA polymerase, and blockade of Uph expression leads to heart defects and embryonic lethality in mice.

doi: 10.1038/nature20128


PI3Kγ is a molecular switch that controls immune suppression p.437

Macrophages play critical, but opposite, roles in acute and chronic inflammation and cancer. In response to pathogens or injury, inflammatory macrophages express cytokines that stimulate cytotoxic T cells, whereas macrophages in neoplastic and parasitic diseases express anti-inflammatory cytokines that induce immune suppression and may promote resistance to T cell checkpoint inhibitors. Here we show that macrophage PI 3-kinase γ controls a critical switch between immune stimulation and suppression during inflammation and cancer. PI3Kγ signalling through Akt and mTor inhibits NFκB activation while stimulating C/EBPβ activation, thereby inducing a transcriptional program that promotes immune suppression during inflammation and tumour growth. By contrast, selective inactivation of macrophage PI3Kγ stimulates and prolongs NFκB activation and inhibits C/EBPβ activation, thus promoting an immunostimulatory transcriptional program that restores CD8+ T cell activation and cytotoxicity. PI3Kγ synergizes with checkpoint inhibitor therapy to promote tumour regression and increased survival in mouse models of cancer. In addition, PI3Kγ-directed, anti-inflammatory gene expression can predict survival probability in cancer patients. Our work thus demonstrates that therapeutic targeting of intracellular signalling pathways that regulate the switch between macrophage polarization states can control immune suppression in cancer and other disorders.

doi: 10.1038/nature19834


Overcoming resistance to checkpoint blockade therapy by targeting PI3Kγ in myeloid cells p.443

Recent clinical trials using immunotherapy have demonstrated its potential to control cancer by disinhibiting the immune system. Immune checkpoint blocking (ICB) antibodies against cytotoxic-T-lymphocyte-associated protein 4 or programmed cell death protein 1/programmed death-ligand 1 have displayed durable clinical responses in various cancers. Although these new immunotherapies have had a notable effect on cancer treatment, multiple mechanisms of immune resistance exist in tumours. Among the key mechanisms, myeloid cells have a major role in limiting effective tumour immunity. Growing evidence suggests that high infiltration of immune-suppressive myeloid cells correlates with poor prognosis and ICB resistance. These observations suggest a need for a precision medicine approach in which the design of the immunotherapeutic combination is modified on the basis of the tumour immune landscape to overcome such resistance mechanisms. Here we employ a pre-clinical mouse model system and show that resistance to ICB is directly mediated by the suppressive activity of infiltrating myeloid cells in various tumours. Furthermore, selective pharmacologic targeting of the gamma isoform of phosphoinositide 3-kinase (PI3Kγ), highly expressed in myeloid cells, restores sensitivity to ICB. We demonstrate that targeting PI3Kγ with a selective inhibitor, currently being evaluated in a phase 1 clinical trial (NCT02637531), can reshape the tumour immune microenvironment and promote cytotoxic-T-cell-mediated tumour regression without targeting cancer cells directly. Our results introduce opportunities for new combination strategies using a selective small molecule PI3Kγ inhibitor, such as IPI-549, to overcome resistance to ICB in patients with high levels of suppressive myeloid cell infiltration in tumours.

doi: 10.1038/nature20554


Alternative modes of client binding enable functional plasticity of Hsp70 p.448

Hsp70 binds unfolded protein segments in its groove, but can also bind and stabilize folded protein structures, owing to its moveable lid, with ATP hydrolysis and co-chaperones allowing control of these contrasting effects.

doi: 10.1038/nature20137


Local regulation of gene expression by lncRNA promoters, transcription and splicing p.452

Various cis-regulatory functions of genomic loci that produce long non-coding RNAs are revealed, including instances where their promoters have enhancer-like activity and the lncRNA transcripts themselves are not required for activity.

doi: 10.1038/nature20149

「Journal home」に戻る