Current Table of Contents

• Making the paper: Marina Wolf
  Unusual brain receptors weaken resistance to cocaine cravings.
• Abstractions
  First authorThe twin Voyager spacecraft, launched in 1977 to travel to and explore Jupiter, Saturn, Uranus and Neptune, have made many intriguing discoveries, including a possible ocean of liquid water on one of Jupiter's moons. On page 71, long-time Voyager project scientist Edward
• From the blogosphere
  A misconduct survey stirs the pot. An Editorial and Commentary in the 19 June issue of Nature (Nature453, 957; 2008 and Nature453, 980–982; 2008) are hotly debated at Nature Network's News and Opinion forum (http://tinyurl.com/5onqpl).
• Feasting and fasting
  Bad nutrition needs the world's attention. Not least that of biologists.
• In rude health
  A treasure-trove of data in the UK National Health Service is set to energize biomedical research.
• Does the past have a future in Berlin?
  Not unless a research institution's managers recognize its value.
• Natural history: Nasty, brutish and short
  Proc. Natl Acad. Sci. USA105, 8980–8984 (2008) Doi:10.1073/pnas.0802468105The Madagascan chameleon Furcifer labordi has an annual life cycle, and spends most of its short life in the egg.Kristopher Karsten of Oklahoma State University in Stillwater
• Neuroscience: Predicting psychosis
  J. Neurosci.28, 6295–6303 (2008) doi:10.1523/JNEUROSCI.0910-08.2008Scientists have found a way of predicting how an individual will respond to the party drug ketamine — and it might help us understand why symptoms of schizophrenia vary so much between
• Genetics: The genetics of anarchy
  Genetics doi: 10.1534/genetics.108.087270 (2008) A study of honeybee 'anarchy' has uncovered several regions of the genome that influence cheating behaviour.Honeybee (Apis mellifera; pictured right) queens emit a pheromone to 'switch off' the ovaries of female worker bees, but
• Chemistry: Flipping brilliant
  Organic Lett. doi: 10.1021/ol801135g (2008A super-fast colour-changing chemical has been synthesized by Jiro Abe and his colleagues at Aoyama Gakuin University in Sagamihara, Japan. The molecule is a ring system containing naphthalene groups.When the colourless version of the molecule is
• Chemical biology: Anti-Alzheimer's agent
  in vivo
• Materials science: The heart of glass
  Nature Mater.7, 556–561 (2008) doi:10.1038/nmat2219A glass is caught somewhere between a liquid and a crystalline solid — its atoms move, but they do so very slowly. Theorists predicted that was because the atoms arranged themselves in
• Genetics: Sex and the cortex
  PLoS Genet.4, e1000100 (2008) doi:10.1371/journal.pgen.1000100How male and female brains differ is debated around the water cooler as much as the lab bench. Working at the latter, Elena Jazin at Uppsala University in Sweden and her colleagues looked for
• Ecology: Drought and the lion
  PLoS ONE3, e2545 (2008)Extreme weather can cause mass die-offs in the animal kingdom by altering host–pathogen relationships, according to researchers led by Craig Packer of the University of Minnesota in St Paul.They found that high lion mortality in Tanzania in 1994
• Acoustics: Fiddling the numbers
  PLoS One3, e2554 (2008)Subtle shifts in density that occur within individual pieces of wood might help to explain why violins made in eighteenth-century Cremona, Italy, sound so special.Berend Stoel, of Leiden University Medical Center in the Netherlands, and Terry Borman, a
• Nanotechnology: Electron windmills
  Phys. Rev. Lett.100, 256802 (2008) doi:10.1103/PhysRevLett.100.256802Carbon nanotubes can be sent spinning by passing an electrical current through them, Steven Bailey and his colleagues at Lancaster University, UK, say.Their calculations show that electrons passing through a nanotube with
• Journal club
  doi:10.1088/1478-3975/5/2/026001A network scientist highlights active sites of enzymes, cells, brains and society.For proteins, chemical binding is a tricky business. Special signals must be sent across a sea of water molecules to the desired partner, and complex mutual structural adjustments (a fluctuation fit)
• Amateurs as an outreach of HAARP's lunar-echo study
  SirYour News Feature 'Heating up the heavens' (Nature452, 930–932; 10.1038/452930a2008) discusses experiments using the High Frequency Active Auroral Research Program (HAARP) facility. I would like to clarify the goal of the lunar-echo experiments.The high power
• Reality lags behind rhetoric in building interdisciplinary work
  SirAs a PhD student in archaeology and genetics, I am all too aware of the difficulties in crossing a gaping discipline divide, as well as of their effect on academic career prospects, as discussed in the Naturejobs article 'Assembly work' (Nature453
• Reduce confusion by using 'design' more intelligently
  SirFew scientists would dispute that evolution provides a far more satisfactory explanation for the workings of living organisms than does 'intelligent design'. But a much more subtle 'design' movement abounds that can distort how they approach their research.According to the Oxford English Dictionary
• Picture not quite worth 1,000 words in this case
  SirIn your News story 'Top billing for platypus at end of evolution tree' (Nature453, 138–139; 2008), the graphic depicting genome status presents a shocking new phylogeny of the Vertebrates — with Archosaurs (birds and crocodilians) and Mammals forming a monophyletic
• Perils of perversity
  Research is riddled with strong characters; Walter Gratzer applauds a spirited attempt to get their measure.
• Bonding as key to hominid origins
  Primatology meets socio-cultural analysis in a controversial account of human evolution.
• Novel alchemy
  
• Hidden Treasures: Institute of Physiology collection
  A cache of beautiful nineteenth-century German scientific devices that has survived many misfortunes now needs a new home, reports Alison Abbott.
• Science and Music: The ear of the beholder
  In the last of nine Essays on science and music, John Sloboda argues that researchers must study music as people actually experience it, if they are to understand how it affects thoughts and feelings.
• Arise 'cliodynamics'
  If we are to learn how to develop a healthy society, we must transform history into an analytical, predictive science, argues Peter Turchin. He has identified intriguing patterns across vastly different times and places.
• Origins of life: How leaky were primitive cells?
  If the first cells were simple vesicles, how did nutrients cross their membranes without help from transport proteins? A model of a primitive cell suggests that early membranes were surprisingly permeable.
• Solar System: A shock for Voyager 2
  The Voyager 2 spacecraft has now followed Voyager 1 into the region beyond the end of the supersonic solar wind, where the influence of interstellar space is growing — so opening a new age of exploration.
• Ecology: Return of the niche
  Two ideas vie for prominence in community ecology — 'niche partitioning' and 'neutral theory'. A survey of patterns of tree abundance in tropical forest prompts fresh thinking on their respective effects.
• Atmospheric chemistry: Her dark materials
  A glitch in the history of sulphur isotopes could imply that methane emitted by the ancient biosphere created a high-altitude photochemical smog, which governed the climate in a distinctly Gaian way.
• Physical chemistry: When molecules don't rebound
  Picture a simple molecule as two balls attached together by a compressible spring. If an incoming atom strikes one end of the molecule, the spring compresses and the vibrating molecule jumps backwards. Or does it?
• Stem cells: Tips for priming potency
  Introducing just four specific genes into adult cells causes them to regress to an embryonic stem-cell-like state. At 1%, the efficiency of this process is low, but two tips are at hand on how to make improvements.
• Climate change: Acid test for marine biodiversity
  Rising levels of atmospheric carbon dioxide lead to acidification of the oceans. A site in the Mediterranean, naturally carbonated by under-sea volcanoes, provides clues to the possible effects on marine ecosystems.
• 50 & 100 Years Ago
  50 years agoAt a meeting of the Linnean Society on July 1, attended by members of the Darwin and Wallace families, representatives of other societies and institutions and members of the Linnean Society, the president, Dr. C. F. A. Pantin, unveiled a plaque in
• Dissecting direct reprogramming through integrative genomic analysis
  Somatic cells can be reprogrammed to a pluripotent state through the ectopic expression of defined transcription factors. Understanding the mechanism and kinetics of this transformation may shed light on the nature of developmental potency and suggest strategies with improved efficiency or safety. Here we report
• SMAD proteins control DROSHA-mediated microRNA maturation
  MicroRNAs (miRNAs) are small non-coding RNAs that participate in the spatiotemporal regulation of messenger RNA and protein synthesis. Aberrant miRNA expression leads to developmental abnormalities and diseases, such as cardiovascular disorders and cancer; however, the stimuli and processes regulating miRNA biogenesis are largely unknown. The
• Cool heliosheath plasma and deceleration of the upstream solar wind at the termination shock
  The solar wind blows outward from the Sun and forms a bubble of solar material in the interstellar medium. The termination shock occurs where the solar wind changes from being supersonic (with respect to the surrounding interstellar medium) to being subsonic. The shock was crossed by Voyager 1 at a heliocentric radius of 94 au (1 au is the Earth–Sun distance) in December 2004 (refs 1–3). The Voyager 2 plasma experiment observed a decrease in solar wind speed commencing on about 9 June 2007, which culminated in several crossings of the termination shock between 30 August and 1 September 2007 (refs 4–7). Since then, Voyager 2 has remained in the heliosheath, the region of shocked solar wind. Here we report observations of plasma at and near the termination shock and in the heliosheath. The heliosphere is asymmetric, pushed inward in the Voyager 2 direction relative to the Voyager 1 direction. The termination shock is a weak, quasi-perpendicular shock that heats the thermal plasma very little. An unexpected finding is that the flow is still supersonic with respect to the thermal ions downstream of the termination shock. Most of the solar wind energy is transferred to the pickup ions or other energetic particles both upstream of and at the termination shock.
• Mediation of the solar wind termination shock by non-thermal ions
  Broad regions on both sides of the solar wind termination shock are populated by high intensities of non-thermal ions and electrons. The pre-shock particles in the solar wind have been measured by the spacecraft Voyager 1 (refs 1–5) and Voyager 2 (refs 3, 6). The post-shock particles in the heliosheath have also been measured by Voyager 1 (refs 3–5). It was not clear, however, what effect these particles might have on the physics of the shock transition until Voyager 2 crossed the shock on 31 August–1 September 2007 (refs 7–9). Unlike Voyager 1, Voyager 2 is making plasma measurements. Data from the plasma and magnetic field instruments on Voyager 2 indicate that non-thermal ion distributions probably have key roles in mediating dynamical processes at the termination shock and in the heliosheath. Here we report that intensities of low-energy ions measured by Voyager 2 produce non-thermal partial ion pressures in the heliosheath that are comparable to (or exceed) both the thermal plasma pressures and the scalar magnetic field pressures. We conclude that these ions are the >0.028 MeV portion of the non-thermal ion distribution that determines the termination shock structure and the acceleration of which extracts a large fraction of bulk-flow kinetic energy from the incident solar wind.
• An asymmetric solar wind termination shock
  Voyager 2 crossed the solar wind termination shock at 83.7 au in the southern hemisphere, ∼10 au closer to the Sun than found by Voyager 1 in the north. This asymmetry could indicate an asymmetric pressure from an interstellar magnetic field, from transient-induced shock motion, or from the solar wind dynamic pressure. Here we report that the intensity of 4–5 MeV protons accelerated by the shock near Voyager 2 was three times that observed concurrently by Voyager 1, indicating differences in the shock at the two locations. (Companion papers report on the plasma, magnetic field, plasma-wave and lower energy particle observations at the shock.) Voyager 2 did not find the source of anomalous cosmic rays at the shock, suggesting that the source is elsewhere on the shock or in the heliosheath. The small intensity gradient of Galactic cosmic ray helium indicates that either the gradient is further out in the heliosheath or the local interstellar Galactic cosmic ray intensity is lower than expected.
• Magnetic fields at the solar wind termination shock
  A transition between the supersonic solar wind and the subsonic heliosheath was observed by Voyager 1, but the expected termination shock was not seen owing to a gap in the telemetry. Here we report observations of the magnetic field structure and dynamics of the termination shock, made by Voyager 2 on 31 August–1 September 2007 at a distance of 83.7 au from the Sun (1 au is the Earth–Sun distance). A single crossing of the shock was expected, with a boundary that was stable on a timescale of several days. But the data reveal a complex, rippled, quasi-perpendicular supercritical magnetohydrodynamic shock of moderate strength undergoing reformation on a scale of a few hours. The observed structure suggests the importance of ionized interstellar atoms (‘pickup protons’) at the shock.
• Intense plasma waves at and near the solar wind termination shock
  Plasma waves are a characteristic feature of shocks in plasmas, and are produced by non-thermal particle distributions that develop in the shock transition layer. The electric fields of these waves have a key role in dissipating energy in the shock and driving the particle distributions back towards thermal equilibrium. Here we report the detection of intense plasma-wave electric fields at the solar wind termination shock. The observations were obtained from the plasma-wave instrument on the Voyager 2 spacecraft. The first evidence of the approach to the shock was the detection of upstream electron plasma oscillations on 1 August 2007 at a heliocentric radial distance of 83.4 au (1 au is the Earth–Sun distance). These narrowband oscillations continued intermittently for about a month until, starting on 31 August 2007 and ending on 1 September 2007, a series of intense bursts of broadband electrostatic waves signalled a series of crossings of the termination shock at a heliocentric radial distance of 83.7 au. The spectrum of these waves is quantitatively similar to those observed at bow shocks upstream of Jupiter, Saturn, Uranus and Neptune.
• Domination of heliosheath pressure by shock-accelerated pickup ions from observations of neutral atoms
  The solar wind blows an immense magnetic bubble, the heliosphere, in the local interstellar medium (mostly neutral gas) flowing by the Sun. Recent measurements by Voyager 2 across the termination shock, where the solar wind is slowed to subsonic speeds before entering the heliosheath, found that the shocked solar wind plasma contains only ∼20 per cent of the energy released by the termination shock, whereas energetic particles above ∼28 keV contain only ∼10 per cent; ∼70 per cent of the energy is unaccounted for, leading to speculation that the unmeasured pickup ions or energetic particles below 28 keV contain the missing energy. Here we report the detection and mapping of heliosheath energetic (∼4–20 keV) neutral atoms produced by charge exchange of suprathermal ions with interstellar neutral atoms. The energetic neutral atoms come from a source ∼60° wide in longitude straddling the direction of the local interstellar medium. Their energy spectra resemble those of solar wind pickup ions, but with a knee at ∼11 keV instead of ∼4 keV, indicating that their parent ions are pickup ions energized by the termination shock. These termination-shock-energized pickup ions contain the missing ∼70 per cent of the energy dissipated in the termination shock, and they dominate the pressure in the heliosheath.
• Spatial cooperativity in soft glassy flows
  Amorphous glassy materials of diverse nature—concentrated emulsions, granular materials, pastes, molecular glasses—display complex flow properties, intermediate between solid and liquid, which are at the root of their use in many applications. A general feature of such systems, well documented yet not really understood, is the strongly nonlinear nature of the flow rule relating stresses and strain rates. Here we use a microfluidic velocimetry technique to characterize the flow of thin layers of concentrated emulsions, confined in gaps of different thicknesses by surfaces of different roughnesses. We find evidence for finite-size effects in the flow behaviour and the absence of an intrinsic local flow rule. In contrast to the classical nonlinearities of the rheological behaviour of amorphous materials, we show that a rather simple non-local flow rule can account for all the velocity profiles. This non-locality of the dynamics is quantified by a length, characteristic of cooperativity within the flow at these scales, that is unobservable in the liquid state (lower emulsion concentrations) and that increases with concentration in the jammed state. Beyond its practical importance for applications involving thin layers (for example, coatings), these non-locality and cooperativity effects have parallels in the behaviour of other glassy, jammed and granular systems, suggesting a possible fundamental universality.
• Vibrational excitation through tug-of-war inelastic collisions
  Vibrationally inelastic scattering is a fundamental collision process that converts some of the kinetic energy of the colliding partners into vibrational excitation,. The conventional wisdom is that collisions with high impact parameters (where the partners only ‘graze’ each other) are forward scattered and essentially elastic, whereas collisions with low impact parameters transfer a large amount of energy into vibrations and are mainly back scattered. Here we report experimental observations of exactly the opposite behaviour for the simplest and most studied of all neutral–neutral collisions: we find that the inelastic scattering process H + D2(v = 0, j = 0, 2) → H + D2(v′ = 3, j′ = 0, 2, 4, 6, 8) leads dominantly to forward scattering (v and j respectively refer to the vibrational and rotational quantum numbers of the D2 molecule). Quasi-classical trajectory calculations show that the vibrational excitation is caused by extension, not compression, of the D–D bond through interaction with the passing H atom. However, the H–D interaction never becomes strong enough for capture of the H atom before it departs with diminished kinetic energy; that is, the inelastic scattering process is essentially a frustrated reaction in which the collision typically excites the outward-going half of the H–D–D symmetric stretch before the H–D2 complex dissociates. We suggest that this ‘tug of war’ between H and D2 is a new mechanism for vibrational excitation that should play a role in all neutral–neutral collisions where strong attraction can develop between the collision partners.
• A light carbon reservoir recorded in zircon-hosted diamond from the Jack Hills
  The recent discovery of diamond–graphite inclusions in the Earth’s oldest zircon grains (formed up to 4,252 Myr ago) from the Jack Hills metasediments in Western Australia provides a unique opportunity to investigate Earth’s earliest known carbon reservoir. Here we report ion microprobe analyses of the carbon isotope composition of these diamond–graphite inclusions. The observed δ13CPDB values (expressed using the PeeDee Belemnite standard) range between -5 per mil and -58 per mil with a median of -31 per mil. This extends beyond typical mantle values of around -6 per mil to values observed in metamorphic and some eclogitic diamonds that are interpreted to reflect deep subduction of low-δ13CPDB biogenic surface carbon. Low δ13CPDB values may also be produced by inorganic chemical reactions, and therefore are not unambiguous evidence for life on Earth as early as 4,250 Myr ago. Regardless, our results suggest that a low-δ13CPDB reservoir may have existed on the early Earth.
• Volcanic carbon dioxide vents show ecosystem effects of ocean acidification
  The atmospheric partial pressure of carbon dioxide (pCO2) will almost certainly be double that of pre-industrial levels by 2100 and will be considerably higher than at any time during the past few million years. The oceans are a principal sink for anthropogenic CO2 where it is estimated to have caused a 30% increase in the concentration of H+ in ocean surface waters since the early 1900s and may lead to a drop in seawater pH of up to 0.5 units by 2100 (refs 2, 3). Our understanding of how increased ocean acidity may affect marine ecosystems is at present very limited as almost all studies have been in vitro, short-term, rapid perturbation experiments on isolated elements of the ecosystem. Here we show the effects of acidification on benthic ecosystems at shallow coastal sites where volcanic CO2 vents lower the pH of the water column. Along gradients of normal pH (8.1–8.2) to lowered pH (mean 7.8–7.9, minimum 7.4–7.5), typical rocky shore communities with abundant calcareous organisms shifted to communities lacking scleractinian corals with significant reductions in sea urchin and coralline algal abundance. To our knowledge, this is the first ecosystem-scale validation of predictions that these important groups of organisms are susceptible to elevated amounts of pCO2. Sea-grass production was highest in an area at mean pH 7.6 (1,827 μatm pCO2) where coralline algal biomass was significantly reduced and gastropod shells were dissolving due to periods of carbonate sub-saturation. The species populating the vent sites comprise a suite of organisms that are resilient to naturally high concentrations of pCO2 and indicate that ocean acidification may benefit highly invasive non-native algal species. Our results provide the first in situ insights into how shallow water marine communities might change when susceptible organisms are removed owing to ocean acidification.
• Extinction risk depends strongly on factors contributing to stochasticity
  Extinction risk in natural populations depends on stochastic factors that affect individuals, and is estimated by incorporating such factors into stochastic models. Stochasticity can be divided into four categories, which include the probabilistic nature of birth and death at the level of individuals (demographic stochasticity), variation in population-level birth and death rates among times or locations (environmental stochasticity), the sex of individuals and variation in vital rates among individuals within a population (demographic heterogeneity). Mechanistic stochastic models that include all of these factors have not previously been developed to examine their combined effects on extinction risk. Here we derive a family of stochastic Ricker models using different combinations of all these stochastic factors, and show that extinction risk depends strongly on the combination of factors that contribute to stochasticity. Furthermore, we show that only with the full stochastic model can the relative importance of environmental and demographic variability, and therefore extinction risk, be correctly determined. Using the full model, we find that demographic sources of stochasticity are the prominent cause of variability in a laboratory population of Tribolium castaneum (red flour beetle), whereas using only the standard simpler models would lead to the erroneous conclusion that environmental variability dominates. Our results demonstrate that current estimates of extinction risk for natural populations could be greatly underestimated because variability has been mistakenly attributed to the environment rather than the demographic factors described here that entail much higher extinction risk for the same variability level.
• A myocardial lineage derives from Tbx18 epicardial cells
  Understanding the origins and roles of cardiac progenitor cells is important for elucidating the pathogenesis of congenital and acquired heart diseases. Moreover, manipulation of cardiac myocyte progenitors has potential for cell-based repair strategies for various myocardial disorders. Here we report the identification in mouse of a previously unknown cardiac myocyte lineage that derives from the proepicardial organ. These progenitor cells, which express the T-box transcription factor Tbx18, migrate onto the outer cardiac surface to form the epicardium, and then make a substantial contribution to myocytes in the ventricular septum and the atrial and ventricular walls. Tbx18-expressing cardiac progenitors also give rise to cardiac fibroblasts and coronary smooth muscle cells. The pluripotency of Tbx18 proepicardial cells provides a theoretical framework for applying these progenitors to effect cardiac repair and regeneration.
• Epicardial progenitors contribute to the cardiomyocyte lineage in the developing heart
  The heart is formed from cardiogenic progenitors expressing the transcription factors Nkx2-5 and Isl1 (refs 1 and 2). These multipotent progenitors give rise to cardiomyocyte, smooth muscle and endothelial cells, the major lineages of the mature heart. Here we identify a novel cardiogenic precursor marked by expression of the transcription factor Wt1 and located within the epicardium—an epithelial sheet overlying the heart. During normal murine heart development, a subset of these Wt1+ precursors differentiated into fully functional cardiomyocytes. Wt1+ proepicardial cells arose from progenitors that express Nkx2-5 and Isl1, suggesting that they share a developmental origin with multipotent Nkx2-5+ and Isl1+ progenitors. These results identify Wt1+ epicardial cells as previously unrecognized cardiomyocyte progenitors, and lay the foundation for future efforts to harness the cardiogenic potential of these progenitors for cardiac regeneration and repair.
• Functional asymmetry in Caenorhabditis elegans taste neurons and its computational role in chemotaxis
  Chemotaxis in Caenorhabditis elegans, like chemotaxis in bacteria, involves a random walk biased by the time derivative of attractant concentration, but how the derivative is computed is unknown. Laser ablations have shown that the strongest deficits in chemotaxis to salts are obtained when the ASE chemosensory neurons (ASEL and ASER) are ablated, indicating that this pair has a dominant role. Although these neurons are left–right homologues anatomically, they exhibit marked asymmetries in gene expression and ion preference. Here, using optical recordings of calcium concentration in ASE neurons in intact animals, we demonstrate an additional asymmetry: ASEL is an ON-cell, stimulated by increases in NaCl concentration, whereas ASER is an OFF-cell, stimulated by decreases in NaCl concentration. Both responses are reliable yet transient, indicating that ASE neurons report changes in concentration rather than absolute levels. Recordings from synaptic and sensory transduction mutants show that the ON–OFF asymmetry is the result of intrinsic differences between ASE neurons. Unilateral activation experiments indicate that the asymmetry extends to the level of behavioural output: ASEL lengthens bouts of forward locomotion (runs) whereas ASER promotes direction changes (turns). Notably, the input and output asymmetries of ASE neurons are precisely those of a simple yet novel neuronal motif for computing the time derivative of chemosensory information, which is the fundamental computation of C. elegans chemotaxis. Evidence for ON and OFF cells in other chemosensory networks suggests that this motif may be common in animals that navigate by taste and smell.
• Formation of accumbens GluR2-lacking AMPA receptors mediates incubation of cocaine craving
  Relapse to cocaine use after prolonged abstinence is an important clinical problem. This relapse is often induced by exposure to cues associated with cocaine use. To account for the persistent propensity for relapse, it has been suggested that cue-induced cocaine craving increases over the first several weeks of abstinence and remains high for extended periods. We and others identified an analogous phenomenon in rats that was termed ‘incubation of cocaine craving’: time-dependent increases in cue-induced cocaine-seeking over the first months after withdrawal from self-administered cocaine. Cocaine-seeking requires the activation of glutamate projections that excite receptors for α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) in the nucleus accumbens. Here we show that the number of synaptic AMPA receptors in the accumbens is increased after prolonged withdrawal from cocaine self-administration by the addition of new AMPA receptors lacking glutamate receptor 2 (GluR2). Furthermore, we show that these new receptors mediate the incubation of cocaine craving. Our results indicate that GluR2-lacking AMPA receptors could be a new target for drug development for the treatment of cocaine addiction. We propose that after prolonged withdrawal from cocaine, increased numbers of synaptic AMPA receptors combined with the higher conductance of GluR2-lacking AMPA receptors causes increased reactivity of accumbens neurons to cocaine-related cues, leading to an intensification of drug craving and relapse.
• Template-directed synthesis of a genetic polymer in a model protocell
  Contemporary phospholipid-based cell membranes are formidable barriers to the uptake of polar and charged molecules ranging from metal ions to complex nutrients. Modern cells therefore require sophisticated protein channels and pumps to mediate the exchange of molecules with their environment. The strong barrier function of membranes has made it difficult to understand the origin of cellular life and has been thought to preclude a heterotrophic lifestyle for primitive cells. Although nucleotides can cross dimyristoyl phosphatidylcholine membranes through defects formed at the gel-to-liquid transition temperature, phospholipid membranes lack the dynamic properties required for membrane growth. Fatty acids and their corresponding alcohols and glycerol monoesters are attractive candidates for the components of protocell membranes because they are simple amphiphiles that form bilayer membrane vesicles that retain encapsulated oligonucleotides and are capable of growth and division. Here we show that such membranes allow the passage of charged molecules such as nucleotides, so that activated nucleotides added to the outside of a model protocell spontaneously cross the membrane and take part in efficient template copying in the protocell interior. The permeability properties of prebiotically plausible membranes suggest that primitive protocells could have acquired complex nutrients from their environment in the absence of any macromolecular transport machinery; that is, they could have been obligate heterotrophs.
• Induced ncRNAs allosterically modify RNA-binding proteins in cis to inhibit transcription
  With the recent recognition of non-coding RNAs (ncRNAs) flanking many genes, a central issue is to obtain a full understanding of their potential roles in regulated gene transcription programmes, possibly through different mechanisms. Here we show that an RNA-binding protein, TLS (for translocated in liposarcoma), serves as a key transcriptional regulatory sensor of DNA damage signals that, on the basis of its allosteric modulation by RNA, specifically binds to and inhibits CREB-binding protein (CBP) and p300 histone acetyltransferase activities on a repressed gene target, cyclin D1 (CCND1) in human cell lines. Recruitment of TLS to the CCND1 promoter to cause gene-specific repression is directed by single-stranded, low-copy-number ncRNA transcripts tethered to the 5′ regulatory regions of CCND1 that are induced in response to DNA damage signals. Our data suggest that signal-induced ncRNAs localized to regulatory regions of transcription units can act cooperatively as selective ligands, recruiting and modulating the activities of distinct classes of RNA-binding co-regulators in response to specific signals, providing an unexpected ncRNA/RNA-binding protein-based strategy to integrate transcriptional programmes.
• When Johnny comes marching home
  Casualties of war.