Sexism has no place in science p.255

doi: 10.1038/522255a

The right climate p.255

doi: 10.1038/522255b

Risky business p.256

doi: 10.1038/522256a

Revived Philae poised to do comet science p.263

doi: 10.1038/522263a

Turkey election results delight scientists p.264

doi: 10.1038/522264a

Anti-ageing pill pushed as bona fide drug p.265

doi: 10.1038/522265a

US ‘export rules’ threaten research p.266

doi: 10.1038/522266a

Graphene booms in factories but lacks a killer app p.268

doi: 10.1038/522268a

Mining the microbial dark matter p.270

doi: 10.1038/522270a

The super materials that could trump graphene p.274

doi: 10.1038/522274a

A Mars-sized exoplanet p.290

doi: 10.1038/522290a

Receptors for selective recycling p.291

doi: 10.1038/nature14532

Round the bend with microwaves p.292

doi: 10.1038/nature14533

The power of positivity p.294

doi: 10.1038/522294a

Growing feedback from ocean carbon to climate p.295

doi: 10.1038/522295a

Aggregates feel the strain p.296

doi: 10.1038/nature14526

Peculiar boron startles again p.297

doi: 10.1038/522297a

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

doi: 10.1038/nature14504

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

doi: 10.1038/nature14445

A novel multiple-stage antimalarial agent that inhibits protein synthesis p.315

doi: 10.1038/nature14451

The mass of the Mars-sized exoplanet Kepler-138 b from transit timing p.321

doi: 10.1038/nature14494

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

doi: 10.1038/nature14479

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

doi: 10.1038/nature14489

An enigmatic plant-eating theropod from the Late Jurassic period of Chile p.331

doi: 10.1038/nature14307

Activating positive memory engrams suppresses depression-like behaviour p.335

doi: 10.1038/nature14514

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

doi: 10.1038/nature14407

Regulation of endoplasmic reticulum turnover by selective autophagy p.354

doi: 10.1038/nature14498

Receptor-mediated selective autophagy degrades the endoplasmic reticulum and the nucleus p.359

doi: 10.1038/nature14506

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

Synthesis and applications of RNAs with position-selective labelling and mosaic composition p.368

doi: 10.1038/nature14352