Volume 522 Number 7556

Editorials

Sexism has no place in science p.255

The comments about women in the laboratory made by Nobel laureate Tim Hunt are a reminder that equality in science is a battle still far from won.

doi: 10.1038/522255a

The right climate p.255

A Republican US presidential candidate speaks on climate change, but will his party listen?

doi: 10.1038/522255b

Risky business p.256

Funding agencies should highlight their roles as risk managers to underpin public trust.

doi: 10.1038/522256a

News

News Features

News & Views

A Mars-sized exoplanet p.290

Analysis of Kepler data has yielded the smallest known mass for an exoplanet orbiting a normal star. Its mass and size are similar to those of Mars, setting a benchmark for the properties of exoplanets smaller than Earth. See Letter p.321

doi: 10.1038/522290a

Receptors for selective recycling p.291

Two studies show that the engulfment of certain intracellular membranous structures by vesicles called autophagosomes regulates the structures' degradation in a selective, receptor-protein-mediated manner. See Letters p.354 & p.359

doi: 10.1038/nature14532

Round the bend with microwaves p.292

Simulations reveal that microwaves propagating through a waveguide can travel around sharp bends in the device without being reflected. The finding might open the way to technologies that exploit this uncommon phenomenon.

doi: 10.1038/nature14533

The power of positivity p.294

Stimulating neurons in the brain's hippocampus that are normally activated by pleasurable experiences protects mice from the depressive consequences of stress. See Letter p.335

doi: 10.1038/522294a

Growing feedback from ocean carbon to climate p.295

The finding that feedbacks between the ocean's carbon cycle and climate may become larger than terrestrial carbon–climate feedbacks has implications for the socio-economic effects of today's fossil-fuel emissions.

doi: 10.1038/522295a

Aggregates feel the strain p.296

Aggregates of α-synuclein protein can form in various cell types and cause different neurodegenerative disorders. The existence of strains with distinct structural conformations might explain this variability. See Letter p.340

doi: 10.1038/nature14526

Peculiar boron startles again p.297

Boron's unusual properties inspired big advances in chemistry. A compound in which boron binds two carbon monoxide molecules reveals another oddity — the element forms bonds similar to those of transition metals. See Letter p.327

doi: 10.1038/522297a

Review

Pacific western boundary currents and their roles in climate p.299

A review of western boundary currents in the Pacific Ocean explores their far-reaching influence on the El Niño/Southern Oscillation, the Indonesian Throughflow, Asian monsoons, and ocean circulation in the South China Sea, and concludes that major conceptual and technical progress will be needed to close the regional mass budget and provide robust projections of Pacific western boundary currents in a changing climate.

doi: 10.1038/nature14504

Articles

Hippocampal–prefrontal input supports spatial encoding in working memory p.309

Spatial working memory is known to involve the prefrontal cortex and the hippocampus, but the specificities of the connection have been unclear; now, a direct path between these two areas is defined that is necessary for the encoding of spatial cues in mice, but is not required for the maintenance or retrieval of these cues.

doi: 10.1038/nature14445

Letters

A permanent, asymmetric dust cloud around the Moon p.324

Observations are reported of a permanent, asymmetric dust cloud around the Moon, caused by impacts of high-speed cometary dust particles on eccentric orbits, as opposed to particles of asteroidal origin following near-circular paths striking the Moon at lower speeds.

doi: 10.1038/nature14479

Multiple complexation of CO and related ligands to a main-group element p.327

Transition metal–ligand fragments are often able to bind and release several carbon monoxide molecules, such as the catalysts used in industrial-scale acetic acid synthesis and the active sites of hydrogenase enzymes, but main-group elements have never shown an ability to bind more than one carbon monoxide molecule; here a boron-based compound stable to moisture and air is synthesized and shown to contain multiple carbon monoxide units bound to the central boron atom.

doi: 10.1038/nature14489

α-Synuclein strains cause distinct synucleinopathies after local and systemic administration p.340

Misfolded protein aggregates represent a continuum with overlapping features in neurodegenerative diseases, but differences in protein components and affected brain regions. The molecular hallmark of synucleinopathies such as Parkinson’s disease, dementia with Lewy bodies and multiple system atrophy are megadalton α-synuclein-rich deposits suggestive of one molecular event causing distinct disease phenotypes. Glial α-synuclein (α-SYN) filamentous deposits are prominent in multiple system atrophy and neuronal α-SYN inclusions are found in Parkinson’s disease and dementia with Lewy bodies. The discovery of α-SYN assemblies with different structural characteristics or ‘strains’ has led to the hypothesis that strains could account for the different clinico-pathological traits within synucleinopathies. In this study we show that α-SYN strain conformation and seeding propensity lead to distinct histopathological and behavioural phenotypes. We assess the properties of structurally well-defined α-SYN assemblies (oligomers, ribbons and fibrils) after injection in rat brain. We prove that α-SYN strains amplify in vivo. Fibrils seem to be the major toxic strain, resulting in progressive motor impairment and cell death, whereas ribbons cause a distinct histopathological phenotype displaying Parkinson’s disease and multiple system atrophy traits. Additionally, we show that α-SYN assemblies cross the blood–brain barrier and distribute to the central nervous system after intravenous injection. Our results demonstrate that distinct α-SYN strains display differential seeding capacities, inducing strain-specific pathology and neurotoxic phenotypes.

doi: 10.1038/nature14547

IL-17-producing γδ T cells and neutrophils conspire to promote breast cancer metastasis p.345

Metastatic disease remains the primary cause of death for patients with breast cancer. The different steps of the metastatic cascade rely on reciprocal interactions between cancer cells and their microenvironment. Within this local microenvironment and in distant organs, immune cells and their mediators are known to facilitate metastasis formation. However, the precise contribution of tumour-induced systemic inflammation to metastasis and the mechanisms regulating systemic inflammation are poorly understood. Here we show that tumours maximize their chance of metastasizing by evoking a systemic inflammatory cascade in mouse models of spontaneous breast cancer metastasis. We mechanistically demonstrate that interleukin (IL)-1β elicits IL-17 expression from gamma delta (γδ) T cells, resulting in systemic, granulocyte colony-stimulating factor (G-CSF)-dependent expansion and polarization of neutrophils in mice bearing mammary tumours. Tumour-induced neutrophils acquire the ability to suppress cytotoxic T lymphocytes carrying the CD8 antigen, which limit the establishment of metastases. Neutralization of IL-17 or G-CSF and absence of γδ T cells prevents neutrophil accumulation and downregulates the T-cell-suppressive phenotype of neutrophils. Moreover, the absence of γδ T cells or neutrophils profoundly reduces pulmonary and lymph node metastases without influencing primary tumour progression. Our data indicate that targeting this novel cancer-cell-initiated domino effect within the immune system—the γδ T cell/IL-17/neutrophil axis—represents a new strategy to inhibit metastatic disease.

doi: 10.1038/nature14282

MET is required for the recruitment of anti-tumoural neutrophils p.349

Whether neutrophils exert an anti- or pro-tumorigenic function has remained controversial; now, expression of the receptor molecule MET in neutrophils is shown to be required for their ability to restrict tumour growth in several mouse cancer models, with potential implications for human cancer therapy.

doi: 10.1038/nature14407

Regulation of endoplasmic reticulum turnover by selective autophagy p.354

The protein FAM134B is an endoplasmic reticulum (ER)-resident receptor that facilitates ER autophagy, and downregulation of this protein (mutations of which are also known to cause sensory neuropathy in humans) results in expanded ER structures and degeneration of mouse sensory neurons.

doi: 10.1038/nature14498

Alternative 3′ UTRs act as scaffolds to regulate membrane protein localization p.363

About half of human genes use alternative cleavage and polyadenylation (ApA) to generate messenger RNA transcripts that differ in the length of their 3′ untranslated regions (3′ UTRs) while producing the same protein. Here we show in human cell lines that alternative 3′ UTRs differentially regulate the localization of membrane proteins. The long 3′ UTR of CD47 enables efficient cell surface expression of CD47 protein, whereas the short 3′ UTR primarily localizes CD47 protein to the endoplasmic reticulum. CD47 protein localization occurs post-translationally and independently of RNA localization. In our model of 3′ UTR-dependent protein localization, the long 3′ UTR of CD47 acts as a scaffold to recruit a protein complex containing the RNA-binding protein HuR (also known as ELAVL1) and SET to the site of translation. This facilitates interaction of SET with the newly translated cytoplasmic domains of CD47 and results in subsequent translocation of CD47 to the plasma membrane via activated RAC1 (ref. 5). We also show that CD47 protein has different functions depending on whether it was generated by the short or long 3′ UTR isoforms. Thus, ApA contributes to the functional diversity of the proteome without changing the amino acid sequence. 3′ UTR-dependent protein localization has the potential to be a widespread trafficking mechanism for membrane proteins because HuR binds to thousands of mRNAs, and we show that the long 3′ UTRs of CD44, ITGA1 and TNFRSF13C, which are bound by HuR, increase surface protein expression compared to their corresponding short 3′ UTRs. We propose that during translation the scaffold function of 3′ UTRs facilitates binding of proteins to nascent proteins to direct their transport or function—and this role of 3′ UTRs can be regulated by ApA.

doi: 10.1038/nature14321