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Nature is the international weekly journal of science: a magazine style journal that publishes full-length research papers in all disciplines of science, as well as News and Views, reviews, news, features, commentaries, web focuses and more, covering all



 



Trump’s vaccine-commission idea is biased and dangerous

2017-01-17

Scientists must fight back with the truth about the debunked link between vaccines and autism.



Replication studies offer much more than technical details

2017-01-18

They demonstrate the practice of science at its best.



Base the social cost of carbon on the science

2017-01-18

The potential economic damage from global warming should not be influenced by politics.



Give the public the tools to trust scientists

2017-01-17

Anita Makri argues that the form of science communicated in popular media leaves the public vulnerable to false certainty.



Animal behaviour: Faecal odours act as rhino signals

2017-01-18

White rhinos can learn about each other by sniffing one another's faeces.Many mammals communicate through smells in their urine. To see whether faeces have a similar role, Courtney Marneweck at the University of KwaZulu-Natal in Pietermaritzburg, South Africa, and her colleagues analysed odours from



Neuroscience: How to turn on killer instinct

2017-01-18

The activation of a particular group of brain cells is all it takes to make mice hunt to kill.The brain's central amygdala has long been thought to have a role in producing emotions, particularly fear. To activate this brain region, Ivan de Araujo at



Chemistry: Molecule gets knotted

2017-01-18

Scientists have braided a molecule into a knot with eight crossings, the most complex yet made in the lab.Flexible polymers can twist themselves into complex knots, but scientists have struggled to create all but the simplest structures. David Leigh and his colleagues at the



Climate change: Sea-level rise for centuries to come

2017-01-18

Atmospheric methane and other short-lived greenhouse gases are set to keep the global sea level rising for several centuries — even after any potential decline or halt in emissions.Greenhouse gases in the atmosphere cause ocean warming and thermal expansion that results in sea-level rise.



Ecology: Trees grow thick skin to survive fire

2017-01-18

Trees that live in fire-prone areas have evolved thick bark to protect themselves. This trait can be used as an indicator of how resilient a tree species is to increased fire risk under global warming.Adam Pellegrini, now at Stanford University in California, and his



Palaeontology: Trilobites laid eggs

2017-01-18

The discovery that extinct marine organisms called trilobites laid eggs provides the first direct evidence for how they reproduced.Trilobites lived between 520 million and 250 million years ago, and are one of the earliest known groups of arthropods (invertebrates, including modern insects, with exoskeletons



Evolution: How menopause emerged in whales

2017-01-18

Differences between the breeding success of mothers and daughters may have driven the evolution of menopause, according to a study on killer whales.Evolutionary biologists have long puzzled over why females of certain species — humans, killer whales and short-finned pilot whales — stop ovulating



Conservation: Pristine forests are shrinking fast

2017-01-18

Less than one-quarter of the world's forests show no obvious signs of human activity, and the proportion of undisturbed forest has dropped markedly since the millennium.Peter Potapov at the University of Maryland in College Park and his co-workers used satellite images to identify areas



Cancer biology: Tumours slowed by diet tweak

2017-01-18

A high-fat diet speeds tumour growth in mice, but this can be counteracted by drugs that lower levels of a metabolite in the blood.Diet can influence cancer survival, but the molecular reasons are largely unknown. Jing Chen at Emory University in Atlanta, Georgia, and



Marijuana's benefits, Antarctic ice cracks and a $500-million donation

2017-01-18

The week in science: 13–19 January 2017.



India’s first GM food crop held up by lawsuit

2017-01-18

Scientists accused of deceiving the public about benefits of transgenic mustard.



Cancer reproducibility project releases first results

2017-01-18

An open-science effort to replicate dozens of cancer-biology studies is off to a confusing start.



Gates Foundation research can’t be published in top journals

2017-01-13

Publications such as Nature and Science have policies that clash with the global health charity's open-access mandate.



Space-weather forecast to improve with European satellite

2017-01-18

Probe could give early warnings of catastrophic solar storms heading for Earth.



US energy agency strengthens protections for scientists

2017-01-11

Revised scientific-integrity policy gives researchers more leeway to speak to the press and publish their findings.



Croatia’s science minister rejects calls to resign amid plagiarism scandal

2017-01-17

Pavo Barišić says he won't step down after a parliamentary ethics committee found he copied another scholar's work.



The $2.4-billion plan to steal a rock from Mars
NASA is now building the rover that it hopes will bring back signs of life on the red planet.



Five big mysteries about CRISPR’s origins

2017-01-12

Where did it come from? How do organisms use it without self-destructing? And what else can it do?



How to turn competitors into collaborators

2017-01-17

Erica Ollmann Saphire and colleagues share lessons in finding treatments fast from the work on Ebola by the Viral Hemorrhagic Fever Immunotherapeutic Consortium.



Technology: He wrote the future

2017-01-18

On Arthur C. Clarke's centenary, Andrew Robinson lauds a prescient, original writer.



Books in brief

2017-01-18

Barbara Kiser reviews five of the week's best science picks.



Brussels Declaration: Twenty-point plan for science policy

2017-01-18

The Brussels Declaration will be published at next month's meeting of the American Association for the Advancement of Science in Boston, Massachusetts. It is a 20-point blueprint for a set of ethics and principles to inform work at the boundaries of science, society and policy.



Anthropocene: its stratigraphic basis

2017-01-18

As officers of the Anthropocene Working Group (AWG; J.Z. and C.W.) and chair of the Subcommission on Quaternary Stratigraphy (SQS; M.J.H.) of the International Commission on Stratigraphy (ICS), we note that the AWG has less power than Erle Ellis and colleagues imply (Nature540



Anthropocene: social science misconstrued

2017-01-18

Adding in a wider range of social-science expertise will not, in my view, help efforts to 'formalize the Anthropocene' as a geological age of human influence (E.Elliset al. Nature540, 192–193;10.1038/540192a2016). The authors rightly



Censorship: Beware scientists wielding red pens

2017-01-18

By inviting scientists to take their 'red pens to the Internet' and grade online sources of science reporting, Phil Williamson implies that science is the primary and final voice in public discussion (Nature540, 171;10.1038/540171a2016). This disregards other ways



John Glenn (1921–2016)

2017-01-18

US astronaut and senator.



Communication: Post-truth predicaments

2017-01-18

How can scientists get through to a public that's seemingly indifferent to objective facts?



Turning point: Advocacy ambassador

2017-01-18

A social-media professional calls on researchers to speak out for their science.



Frontiers in biology

2017-01-18

The Nature Insight 'Frontiers in Biology' aims to cover timely and important developments across biology, ranging from molecular mechanisms to whole-organism physiology and biomedicine.Improvements in sequencing and in methods for enriching and extracting ancient DNA have furthered the temporal and geographic reach of



Tracing the peopling of the world through genomics

2017-01-18

Advances in the sequencing and the analysis of the genomes of both modern and ancient peoples have facilitated a number of breakthroughs in our understanding of human evolutionary history. These include the discovery of interbreeding between anatomically modern humans and extinct hominins; the development of



From morphogen to morphogenesis and back

2017-01-18

A long-term aim of the life sciences is to understand how organismal shape is encoded by the genome. An important challenge is to identify mechanistic links between the genes that control cell-fate decisions and the cellular machines that generate shape, therefore closing the gap between



Elements of cancer immunity and the cancer–immune set point

2017-01-18

Immunotherapy is proving to be an effective therapeutic approach in a variety of cancers. But despite the clinical success of antibodies against the immune regulators CTLA4 and PD-L1/PD-1, only a subset of people exhibit durable responses, suggesting that a broader view of cancer immunity is



Scaling single-cell genomics from phenomenology to mechanism

2017-01-18

Three of the most fundamental questions in biology are how individual cells differentiate to form tissues, how tissues function in a coordinated and flexible fashion and which gene regulatory mechanisms support these processes. Single-cell genomics is opening up new ways to tackle these questions by



Chemical and structural effects of base modifications in messenger RNA

2017-01-18

A growing number of nucleobase modifications in messenger RNA have been revealed through advances in detection and RNA sequencing. Although some of the biochemical pathways that involve modified bases have been identified, research into the world of RNA modification — the epitranscriptome — is still



Cease and desist

2017-01-18

Our word is your bond.



Correction

2017-01-17

The Comment ‘Involve social scientists in defining the Anthropocene’ (E. Ellis et al. Nature540, 192–193; 2016) incorrectly stated that proposals for defining this epoch will be put forward for ratification by the International Geological Congress. In fact, they will be put to



Quantum optics: Quiet moments in time

2017-01-18

'Squeezed' light exhibits smaller quantum fluctuations than no light at all. Localized squeezed regions have now been produced along an infrared light wave and probed with unprecedented time resolution. See Letter p.376



Molecular biology: Messenger RNAs marked for longer life

2016-12-21

A molecular modification called m6Am has been found to regulate the stability of messenger RNAs in mammalian cells. The mechanism casts fresh light on how reversibly modified RNA bases control the fate of mRNA. See Article p.371



Human behaviour: Shoppers like what they know

2017-01-11

Faced with ever-changing products, consumers can benefit from trying new items. But data collected over almost five years show that, the longer shoppers have been buying a favourite product, the more likely they are to stick with it.



Reconfigurable materials: Algorithm for architectural origami

2017-01-18

An algorithm has been developed allowing the rational design of origami-inspired materials that can be rearranged to change their properties. This might open the way to strategies for making reconfigurable robots. See Article p.347



Microbiology: Mind the gaps in cellular evolution

2017-01-11

Eukaryotic cells, with complex features such as membrane-bound nuclei, evolved from prokaryotic cells that lack these components. A newly identified prokaryotic group reveals intermediate steps in eukaryotic-cell evolution. See Article p.353



Virology: Ins and outs of picornaviruses

2017-01-11

Competition between the phospholipase enzyme PLA2G16 and the protein galectin-8 determines whether the RNA-based genomes of picornaviruses can be effectively delivered into host cells. See Letter p.412



50 & 100 Years Ago

2017-01-18

50 Years AgoWhen spiders are given lysergic acid they construct webs of more than usual regularity; they become, like man in a similar situation, withdrawn from external stimuli so that their perceptive awareness is reduced, and they cease to adjust their webs to the



Rational design of reconfigurable prismatic architected materials

2017-01-18

Advances in fabrication technologies are enabling the production of architected materials with unprecedented properties. Most such materials are characterized by a fixed geometry, but in the design of some materials it is possible to incorporate internal mechanisms capable of reconfiguring their spatial architecture, and in



Asgard archaea illuminate the origin of eukaryotic cellular complexity

2017-01-11

The origin and cellular complexity of eukaryotes represent a major enigma in biology. Current data support scenarios in which an archaeal host cell and an alphaproteobacterial (mitochondrial) endosymbiont merged together, resulting in the first eukaryotic cell. The host cell is related to Lokiarchaeota, an archaeal



Genomic hallmarks of localized, non-indolent prostate cancer

2017-01-09

Prostate tumours are highly variable in their response to therapies, but clinically available prognostic factors can explain only a fraction of this heterogeneity. Here we analysed 200 whole-genome sequences and 277 additional whole-exome sequences from localized, non-indolent prostate tumours with similar clinical risk profiles, and



Integration of temporal and spatial patterning generates neural diversity

2017-01-11

In the Drosophila optic lobes, 800 retinotopically organized columns in the medulla act as functional units for processing visual information. The medulla contains over 80 types of neuron, which belong to two classes: uni-columnar neurons have a stoichiometry of one per column, while multi-columnar



Reversible methylation of m6Am in the 5′ cap controls mRNA stability

2016-12-21

Internal bases in mRNA can be subjected to modifications that influence the fate of mRNA in cells. One of the most prevalent modified bases is found at the 5′ end of mRNA, at the first encoded nucleotide adjacent to the 7-methylguanosine cap. Here we show



Subcycle quantum electrodynamics

2017-01-18

Squeezed states of electromagnetic radiation have quantum fluctuations below those of the vacuum field. They offer a unique resource for quantum information systems and precision metrology, including gravitational wave detectors, which require unprecedented sensitivity. Since the first experiments on this non-classical form of light, quantum analysis has been based on homodyning techniques and photon correlation measurements. These methods currently function in the visible to near-infrared and microwave spectral ranges. They require a well-defined carrier frequency, and photons contained in a quantum state need to be absorbed or amplified. Quantum non-demolition experiments may be performed to avoid the influence of a measurement in one quadrature, but this procedure comes at the expense of increased uncertainty in another quadrature. Here we generate mid-infrared time-locked patterns of squeezed vacuum noise. After propagation through free space, the quantum fluctuations of the electric field are studied in the time domain using electro-optic sampling with few-femtosecond laser pulses. We directly compare the local noise amplitude to that of bare (that is, unperturbed) vacuum. Our nonlinear approach operates off resonance and, unlike homodyning or photon correlation techniques, without absorption or amplification of the field that is investigated. We find subcycle intervals with noise levels that are substantially less than the amplitude of the vacuum field. As a consequence, there are enhanced fluctuations in adjacent time intervals, owing to Heisenberg’s uncertainty principle, which indicate generation of highly correlated quantum radiation. Together with efforts in the far infrared, this work enables the study of elementary quantum dynamics of light and matter in an energy range at the boundary between vacuum and thermal background conditions.



Kinetically E-selective macrocyclic ring-closing metathesis

2017-01-09

Macrocyclic compounds are central to the development of new drugs, but preparing them can be challenging because of the energy barrier that must be surmounted in order to bring together and fuse the two ends of an acyclic precursor such as an alkene (also known as an olefin). To this end, the catalytic process known as ring-closing metathesis (RCM) has allowed access to countless biologically active macrocyclic organic molecules, even for large-scale production. Stereoselectivity is often critical in such cases: the potency of a macrocyclic compound can depend on the stereochemistry of its alkene; alternatively, one isomer of the compound can be subjected to stereoselective modification (such as dihydroxylation). Kinetically controlled Z-selective RCM reactions have been reported, but the only available metathesis approach for accessing macrocyclic E-olefins entails selective removal of the Z-component of a stereoisomeric mixture by ethenolysis, sacrificing substantial quantities of material if E/Z ratios are near unity. Use of ethylene can also cause adventitious olefin isomerization—a particularly serious problem when the E-alkene is energetically less favoured. Here, we show that dienes containing an E-alkenyl–B(pinacolato) group, widely used in catalytic cross-coupling, possess the requisite electronic and steric attributes to allow them to be converted stereoselectively to E-macrocyclic alkenes. The reaction is promoted by a molybdenum monoaryloxide pyrrolide complex and affords products at a yield of up to 73 per cent and an E/Z ratio greater than 98/2. We highlight the utility of the approach by preparing recifeiolide (a 12-membered-ring antibiotic) and pacritinib (an 18-membered-ring enzyme inhibitor), the Z-isomer of which is less potent than the E-isomer. Notably, the 18-membered-ring moiety of pacritinib—a potent anti-cancer agent that is in advanced clinical trials for treating lymphoma and myelofibrosis—was prepared by RCM carried out at a substrate concentration 20 times greater than when a ruthenium carbene was used.



Evolution of the global phosphorus cycle

2016-12-21

The macronutrient phosphorus is thought to limit primary productivity in the oceans on geological timescales. Although there has been a sustained effort to reconstruct the dynamics of the phosphorus cycle over the past 3.5 billion years, it remains uncertain whether phosphorus limitation persisted throughout Earth’s history and therefore whether the phosphorus cycle has consistently modulated biospheric productivity and ocean–atmosphere oxygen levels over time. Here we present a compilation of phosphorus abundances in marine sedimentary rocks spanning the past 3.5 billion years. We find evidence for relatively low authigenic phosphorus burial in shallow marine environments until about 800 to 700 million years ago. Our interpretation of the database leads us to propose that limited marginal phosphorus burial before that time was linked to phosphorus biolimitation, resulting in elemental stoichiometries in primary producers that diverged strongly from the Redfield ratio (the atomic ratio of carbon, nitrogen and phosphorus found in phytoplankton). We place our phosphorus record in a quantitative biogeochemical model framework and find that a combination of enhanced phosphorus scavenging in anoxic, iron-rich oceans and a nutrient-based bistability in atmospheric oxygen levels could have resulted in a stable low-oxygen world. The combination of these factors may explain the protracted oxygenation of Earth’s surface over the last 3.5 billion years of Earth history. However, our analysis also suggests that a fundamental shift in the phosphorus cycle may have occurred during the late Proterozoic eon (between 800 and 635 million years ago), coincident with a previously inferred shift in marine redox states, severe perturbations to Earth’s climate system, and the emergence of animals.



Hurricane intensification along United States coast suppressed during active hurricane periods

2017-01-04

The North Atlantic ocean/atmosphere environment exhibits pronounced interdecadal variability that is known to strongly modulate Atlantic hurricane activity. Variability in sea surface temperature (SST) is correlated with hurricane variability through its relationship with the genesis and thermodynamic potential intensity of hurricanes. Another key factor that governs the genesis and intensity of hurricanes is ambient environmental vertical wind shear (VWS). Warmer SSTs generally correlate with more frequent genesis and greater potential intensity, while VWS inhibits genesis and prevents any hurricanes that do form from reaching their potential intensity. When averaged over the main hurricane-development region in the Atlantic, SST and VWS co-vary inversely, so that the two factors act in concert to either enhance or inhibit basin-wide hurricane activity. Here I show, however, that conditions conducive to greater basin-wide Atlantic hurricane activity occur together with conditions for more probable weakening of hurricanes near the United States coast. Thus, the VWS and SST form a protective barrier along the United States coast during periods of heightened basin-wide hurricane activity. Conversely, during the most-recent period of basin-wide quiescence, hurricanes (and particularly major hurricanes) near the United States coast, although substantially less frequent, exhibited much greater variability in their rate of intensification, and were much more likely to intensify rapidly. Such heightened variability poses greater challenges to operational forecasting and, consequently, greater coastal risk during hurricane events.



Hyoliths are Palaeozoic lophophorates

2017-01-11

Hyoliths are abundant and globally distributed ‘shelly’ fossils that appear early in the Cambrian period and can be found throughout the 280 million year span of Palaeozoic strata. The ecological and evolutionary importance of this group has remained unresolved, largely because of their poorly constrained soft anatomy and idiosyncratic scleritome, which comprises an operculum, a conical shell and, in some taxa, a pair of lateral spines (helens). Since their first description over 175 years ago, hyoliths have most often been regarded as incertae sedis, related to molluscs or assigned to their own phylum. Here we examine over 1,500 specimens of the mid-Cambrian hyolith Haplophrentis from the Burgess Shale and Spence Shale Lagerstätten. We reconstruct Haplophrentis as a semi-sessile, epibenthic suspension feeder that could use its helens to elevate its tubular body above the sea floor. Exceptionally preserved soft tissues include an extendable, gullwing-shaped, tentacle-bearing organ surrounding a central mouth, which we interpret as a lophophore, and a U-shaped digestive tract ending in a dorsolateral anus. Together with opposing bilateral sclerites and a deep ventral visceral cavity, these features indicate an affinity with the lophophorates (brachiopods, phoronids and tommotiids), substantially increasing the morphological disparity of this prominent group.



A theoretical foundation for multi-scale regular vegetation patterns

2017-01-18

Self-organized regular vegetation patterns are widespread and thought to mediate ecosystem functions such as productivity and robustness, but the mechanisms underlying their origin and maintenance remain disputed. Particularly controversial are landscapes of overdispersed (evenly spaced) elements, such as North American Mima mounds, Brazilian murundus, South African heuweltjies, and, famously, Namibian fairy circles. Two competing hypotheses are currently debated. On the one hand, models of scale-dependent feedbacks, whereby plants facilitate neighbours while competing with distant individuals, can reproduce various regular patterns identified in satellite imagery. Owing to deep theoretical roots and apparent generality, scale-dependent feedbacks are widely viewed as a unifying and near-universal principle of regular-pattern formation despite scant empirical evidence. On the other hand, many overdispersed vegetation patterns worldwide have been attributed to subterranean ecosystem engineers such as termites, ants, and rodents. Although potentially consistent with territorial competition, this interpretation has been challenged theoretically and empirically and (unlike scale-dependent feedbacks) lacks a unifying dynamical theory, fuelling scepticism about its plausibility and generality. Here we provide a general theoretical foundation for self-organization of social-insect colonies, validated using data from four continents, which demonstrates that intraspecific competition between territorial animals can generate the large-scale hexagonal regularity of these patterns. However, this mechanism is not mutually exclusive with scale-dependent feedbacks. Using Namib Desert fairy circles as a case study, we present field data showing that these landscapes exhibit multi-scale patterning—previously undocumented in this system—that cannot be explained by either mechanism in isolation. These multi-scale patterns and other emergent properties, such as enhanced resistance to and recovery from drought, instead arise from dynamic interactions in our theoretical framework, which couples both mechanisms. The potentially global extent of animal-induced regularity in vegetation—which can modulate other patterning processes in functionally important ways—emphasizes the need to integrate multiple mechanisms of ecological self-organization.



Genetic variants regulating expression levels and isoform diversity during embryogenesis

2016-12-26

Embryonic development is driven by tightly regulated patterns of gene expression, despite extensive genetic variation among individuals. Studies of expression quantitative trait loci (eQTL) indicate that genetic variation frequently alters gene expression in cell-culture models and differentiated tissues. However, the extent and types of genetic variation impacting embryonic gene expression, and their interactions with developmental programs, remain largely unknown. Here we assessed the effect of genetic variation on transcriptional (expression levels) and post-transcriptional (3′ RNA processing) regulation across multiple stages of metazoan development, using 80 inbred Drosophila wild isolates, identifying thousands of developmental-stage-specific and shared QTL. Given the small blocks of linkage disequilibrium in Drosophila, we obtain near base-pair resolution, resolving causal mutations in developmental enhancers, validated transcription-factor-binding sites and RNA motifs. This fine-grain mapping uncovered extensive allelic interactions within enhancers that have opposite effects, thereby buffering their impact on enhancer activity. QTL affecting 3′ RNA processing identify new functional motifs leading to transcript isoform diversity and changes in the lengths of 3′ untranslated regions. These results highlight how developmental stage influences the effects of genetic variation and uncover multiple mechanisms that regulate and buffer expression variation during embryogenesis.



Structural basis for nutrient acquisition by dominant members of the human gut microbiota

2017-01-11

The human large intestine is populated by a high density of microorganisms, collectively termed the colonic microbiota, which has an important role in human health and nutrition. The survival of microbiota members from the dominant Gram-negative phylum Bacteroidetes depends on their ability to degrade dietary glycans that cannot be metabolized by the host. The genes encoding proteins involved in the degradation of specific glycans are organized into co-regulated polysaccharide utilization loci, with the archetypal locus sus (for starch utilisation system) encoding seven proteins, SusA–SusG. Glycan degradation mainly occurs intracellularly and depends on the import of oligosaccharides by an outer membrane protein complex composed of an extracellular SusD-like lipoprotein and an integral membrane SusC-like TonB-dependent transporter. The presence of the partner SusD-like lipoprotein is the major feature that distinguishes SusC-like proteins from previously characterized TonB-dependent transporters. Many sequenced gut Bacteroides spp. encode over 100 SusCD pairs, of which the majority have unknown functions and substrate specificities. The mechanism by which extracellular substrate binding by SusD proteins is coupled to outer membrane passage through their cognate SusC transporter is unknown. Here we present X-ray crystal structures of two functionally distinct SusCD complexes purified from Bacteroides thetaiotaomicron and derive a general model for substrate translocation. The SusC transporters form homodimers, with each β-barrel protomer tightly capped by SusD. Ligands are bound at the SusC–SusD interface in a large solvent-excluded cavity. Molecular dynamics simulations and single-channel electrophysiology reveal a ‘pedal bin’ mechanism, in which SusD moves away from SusC in a hinge-like fashion in the absence of ligand to expose the substrate-binding site to the extracellular milieu. These data provide mechanistic insights into outer membrane nutrient import by members of the microbiota, an area of major importance for understanding human–microbiota symbiosis.



PLA2G16 represents a switch between entry and clearance of Picornaviridae

2017-01-11

Picornaviruses are a leading cause of human and veterinary infections that result in various diseases, including polio and the common cold. As archetypical non-enveloped viruses, their biology has been extensively studied. Although a range of different cell-surface receptors are bound by different picornaviruses, it is unclear whether common host factors are needed for them to reach the cytoplasm. Using genome-wide haploid genetic screens, here we identify the lipid-modifying enzyme PLA2G16 (refs 8, 9, 10, 11) as a picornavirus host factor that is required for a previously unknown event in the viral life cycle. We find that PLA2G16 functions early during infection, enabling virion-mediated genome delivery into the cytoplasm, but not in any virion-assigned step, such as cell binding, endosomal trafficking or pore formation. To resolve this paradox, we screened for suppressors of the ΔPLA2G16 phenotype and identified a mechanism previously implicated in the clearance of intracellular bacteria. The sensor of this mechanism, galectin-8 (encoded by LGALS8), detects permeated endosomes and marks them for autophagic degradation, whereas PLA2G16 facilitates viral genome translocation and prevents clearance. This study uncovers two competing processes triggered by virus entry: activation of a pore-activated clearance pathway and recruitment of a phospholipase to enable genome release.



Microenvironmental autophagy promotes tumour growth

2017-01-11

As malignant tumours develop, they interact intimately with their microenvironment and can activate autophagy, a catabolic process which provides nutrients during starvation. How tumours regulate autophagy in vivo and whether autophagy affects tumour growth is controversial. Here we demonstrate, using a well characterized Drosophila melanogaster malignant tumour model, that non-cell-autonomous autophagy is induced both in the tumour microenvironment and systemically in distant tissues. Tumour growth can be pharmacologically restrained using autophagy inhibitors, and early-stage tumour growth and invasion are genetically dependent on autophagy within the local tumour microenvironment. Induction of autophagy is mediated by Drosophila tumour necrosis factor and interleukin-6-like signalling from metabolically stressed tumour cells, whereas tumour growth depends on active amino acid transport. We show that dormant growth-impaired tumours from autophagy-deficient animals reactivate tumorous growth when transplanted into autophagy-proficient hosts. We conclude that transformed cells engage surrounding normal cells as active and essential microenvironmental contributors to early tumour growth through nutrient-generating autophagy.



The role of interfacial lipids in stabilizing membrane protein oligomers

2017-01-11

Oligomerization of membrane proteins in response to lipid binding has a critical role in many cell-signalling pathways but is often difficult to define or predict. Here we report the development of a mass spectrometry platform to determine simultaneously the presence of interfacial lipids and oligomeric stability and to uncover how lipids act as key regulators of membrane-protein association. Evaluation of oligomeric strength for a dataset of 125 α-helical oligomeric membrane proteins reveals an absence of interfacial lipids in the mass spectra of 12 membrane proteins with high oligomeric stability. For the bacterial homologue of the eukaryotic biogenic transporters (LeuT, one of the proteins with the lowest oligomeric stability), we found a precise cohort of lipids within the dimer interface. Delipidation, mutation of lipid-binding sites or expression in cardiolipin-deficient Escherichia coli abrogated dimer formation. Molecular dynamics simulation revealed that cardiolipin acts as a bidentate ligand, bridging across subunits. Subsequently, we show that for the Vibrio splendidus sugar transporter SemiSWEET, another protein with low oligomeric stability, cardiolipin shifts the equilibrium from monomer to functional dimer. We hypothesized that lipids are essential for dimerization of the Na+/H+ antiporter NhaA from E. coli, which has the lowest oligomeric strength, but not for the substantially more stable homologous Thermus thermophilus protein NapA. We found that lipid binding is obligatory for dimerization of NhaA, whereas NapA has adapted to form an interface that is stable without lipids. Overall, by correlating interfacial strength with the presence of interfacial lipids, we provide a rationale for understanding the role of lipids in both transient and stable interactions within a range of α-helical membrane proteins, including G-protein-coupled receptors.