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NEWS & VIEWS NATURE|Vol 463|11 February 2010 in the course of their journey have discovered various superheavy elements, the latest being ununoctium, with 118 protons. However, we cannot be certain that this is the heaviest element. And progress towards setting foot on the island of stability is slow because of the painfully low rates, sometimes only one atom per week, at which these exotic atoms can be produced. The more difficult the synthesis of heavier elements and the production of their isotopes, the more important is the availability of better information on their properties, either through direct measurements or by better theoretical prediction. The accurate knowledge of masses is particularly critical. Einstein’s mass–energy equivalence relates the mass of an isotope directly to how strongly its protons and neutrons are bound; that in turn determines whether it can exist and its lifetime before it decays. This is where Block and colleagues1 have achieved a breakthrough — by performing the first direct mass measurement on the isotopes of a trans-uranium element and by providing the information needed to build a bridge to the island of stability. Furthermore, they have demonstrated that the technique chosen is indeed the most promising one for meeting the challenge of determining the masses of isotopes of superheavy elements. Block et al. determined the masses of the isotopes 252No, 253No and 254No of nobelium. The result achieved for 253No led to a tenfold improvement in the accuracy of its mass, and as a consequence, to an improved knowledge of the masses of all isotopes in the α-decay chain of which it is a member. An α-decay chain is a sequence of radioactive decays in which elements transform into one another by emitting an α-particle. The measurements were performed with SHIPTRAP, a facility specifically developed for high-precision experiments using trapped ions of very heavy and superheavy elements. For the mass determination, powerful Penning-trap mass spectrometry6 was used. In a Penning trap, charged particles can be confined and stored in a strong magnetic field under vacuum for long periods of time. The frequency of the circular, ‘cyclotron’ motion performed by a trapped ion is connected to its charge, its mass and the magnetic-field strength. By determining this frequency, it is possible to obtain the ion’s mass. Such mass measurements can reach extremely high precision — relative uncertainties of less than one part in a billion have been achieved for stable ions7. The real challenge in applying this approach to superheavy elements is reaching a high enough efficiency in transferring these rare isotopes as ions into the trap. Here1, SHIPTRAP has set a new record for the lowest production rate for which a Penning trap has been successfully used to measure the mass of an unstable isotope. Until now, superheavy elements were identified by their indirect connection by α-decay chains to known elements around uranium. Penning-trap mass measurements can tie down loose decay chains that are not yet connected to known elements. Block and colleagues’ first direct mass measurements provide firm anchor points that are much closer to the superheavy elements than before, in addition to improving the accuracy of the mass values for all isotopes in these chains. And such Penning-trap mass measurements1 may become even more important in the long term. As the island of stability is approached, the lifetime of the nuclides is expected to become longer with the addition of more neutrons. Theory predicts half-lives as long as minutes to hours, a trend that is supported by experiments. For half-lives this long, the identification of superheavy elements on the basis of the radioactive decay of their isotopes will no longer be feasible. Identifying new superheavies by weighing them in a Penning trap may then be the only practical approach. ■ Georg Bollen is at the Facility for Rare Isotope Beams, Michigan State University, Michigan 48824-1321, USA. e-mail: [email protected] 1. Block, M. et al. Nature 463, 785–788 (2010). 2. Hofmann, S. & Münzenberg, G. Rev. Mod. Phys. 72, 733–767 (2000). 3. Morita, K. et al. J. Phys. Soc. Jpn 73, 2593–2596 (2004). 4. Oganessian, Y. J. Phys. G 34, R165–R242 (2007). 5. Stavsetra, L. et al. Phys. Rev. Lett. 103, 132502 (2009). 6. Blaum, K. Phys. Rep. 425, 1–78 (2006). 7. Redshaw, M., Mount, B. J., Myers, E. G. & Avignone, F. T. III Phys. Rev. Lett. 102, 212502 (2009). PALAEONTOLOGY Decay distorts ancestry Derek E. G. Briggs Experiments with simple chordate animals show how decay may make the resulting fossils seem less evolved. The consequence is to distort evidence of the evolution of the earliest vertebrates and their precursors. Just as human corpses become more difficult to identify as information is lost through decay, so too do the fossils of our marine ancestors from back in the Cambrian. For example, a remarkable diversity of soft-bodied, fishlike fossils, dating to about 525 million years ago, have been described from Chengjiang in China. Uncertainties about the nature of these creatures, however, have fuelled controversies about their place in the early evolution of chordates, the group that includes all vertebrates and some closely related invertebrates. On page 797 of this issue, Sansom and colleagues1 describe laboratory observations of the decay of two living forms similar to these earliest chordates: the lancelet Branchiostoma (a fish-like invertebrate that has a stiffened structure called the notochord) and the larva of the more familiar lamprey. They find that decomposition of these two creatures always occurs in more or less the same sequence. Features of the head, for example, tend to be Chordates Vertebrates Lamprey (juvenile) Decay Stem vertebrate Decay Stem chordate Figure 1 | ‘Stem-ward slippage.’ Decomposition and the loss of morphological features have the effect of making a fossil seem less evolved than the organism was in life, and therefore closer to an ancestral (stem) position on an evolutionary tree. This simplified version of the chordate tree shows (left to right) outlines of representatives of the cephalochordates and urochordates, and three branches of the vertebrate lineage. Sansom and colleagues’ decay experiments1 with juvenile lampreys show that the progressive loss of features would lead to interpretation of the resultant fossil as a stem vertebrate and then a stem chordate. (Figure based on Fig. 3 of ref. 1.) © 2010 Macmillan Publishers Limited. All rights reserved 741 NATURE|Vol 463|11 February 2010 lost before those of the trunk, fossils, even when the original including the notochord and morphology is unknown. There a muscle blocks. is a long history of palaeontoloEven more strikingly, the gists making observations of appearance of the carcass is transdecay in living organisms in the formed by decay until it resembles laboratory or the field in order to the much simpler morphology understand what is preserved in of an ancestral (stem) chordate. similar fossils7. Ranking tissues Attributes tend to disappear according to how easily they in the opposite order to that in degrade may allow an estimate which they evolved, so that only of how much decay has preceded b the more ancestral morpholfossilization. Recognizing levels ogy remains. As a result, the of susceptibility to decay may corresponding fossil falls in a serve to separate features that misleadingly low position on the have been lost through decompochordate evolutionary tree. This sition from those that were absent process of ‘stem-ward slippage’, in the first place, a distinction as Sansom et al.1 call it, clearly that may be crucial in constraincompromises the usefulness Figure 2 | Early Cambrian yunnanozoan. a, This specimen is well preserved, ing the place of a fossil on the of such fossils in revealing the but, like others from the Chengjiang biota, it is flattened in shale. The chordate tree. pattern of early chordate evolu- orientation of the animal in the rock and the amount of decay before The unfamiliar appearance fossilization vary between examples. Scale bar, 10 mm. b, A reconstruction tion (Fig. 1). of Cambrian creatures may also of the animal in life. The fossil record of early generate another uncertainty chordates poses a challenge to — what is the most appropriate palaeontologists because they predate the details of Chengjiang specimens, for example, living organism for comparison, and how do evolution of the vertebrate skeleton and are are often preserved as a thin layer of pyrite we equate the different features of the fossil consequently soft-bodied. Their lack of hard (iron sulphide, often later replaced by iron with those in living animals to determine the parts means that they fossilize only in extraordi- oxide), which forms as a result of the activity place of the extinct form6? This may boil down nary circumstances; early chordates have been of sulphate-reducing bacteria5. The infor- to questions as fundamental as whether a linear discovered in some of the most famous Cam- mation available depends on a race between structure is the gut or the notochord. Sansom brian fossil deposits such as Chengjiang2, and decay and fossilization. Effects created during and colleagues’ analysis1 offers a cautionary the Burgess Shale near Field in British Colum- decay and preservation may account for some tale for those who would interpret soft-bodied bia3. Such fossils are flattened on the surface of of the controversy surrounding the placement fossils, but the result provides no panacea for the shale and are consequently difficult to inter- of the Chengjiang chordates6. For example, the problem of placing these extinct forms pret (Fig. 2). They have also undergone some as depicted by the red shading in Figure 1a on the tree of life. We still need to rely on selectdecay — the details that survive depend on just of Sansom and colleagues’ paper1 on page 798, ing the most informative fossils and avoiding how much decomposition occurred before the bizarre yunnanozoans have been inter- preconceived ideas about the nature of the fossilization. preted variously as stem deuterostomes, stem animal and the features of its anatomy. Ironically, however, microbial decay is often hemichordates, stem chordates, stem cephaloIs stem-ward slippage just an isolated an essential driver of the preservation process, chordates and stem vertebrates. palaeontological example of Murphy’s law — particularly where fossilization involves the Decay is the norm, and researchers must take in this case, that the most useful evidence is rapid precipitation of minerals4. Morphological it into account when interpreting soft-bodied least likely to be preserved — relevant only to COSMOLOGY Census at a distance Cosmologists have long been occupied with trying to understand how galaxies formed and evolved into their intricate shapes and forms. With François Hammer and colleagues’ results of a comparative census of galaxy types at two different epochs in the Universe’s history, they will become even busier (R. Delgado-Serrano et al. Astron. Astrophys. 509, A78; 2010). In his early-twentieth-century classification scheme, Edwin Hubble categorized the galaxies seen in today’s Universe into three groups according to their visual appearance: ellipticals, spirals and 742 lenticulars (the last being an intermediate type between the first two). Odd-shaped assemblies of gas, stars and dust that don’t fall into any of these categories are termed peculiars. But is the census of today’s Hubble galaxies similar to that of moderately distant galaxies? The conventional view has been that it is. Surprisingly, Hammer and colleagues’ scrutiny of two samples — 148 galaxies selected from the Great Observatories Origins Deep Survey, seen as they were 6 billion years ago, and 116 local galaxies from the Sloan Digital Sky Survey — finds that it isn’t. The authors demonstrate that, in the distant sample, the fraction of © 2010 Macmillan Publishers Limited. All rights reserved peculiar galaxies (pictured) is about five times higher than that of their present-day counterparts, and that spirals were about 2.3 times less abundant. In striking contrast, the number of ellipticals and lenticulars is essentially the same. But there’s much more to Hammer and colleagues’ study than counting galaxies and sorting them into classes. Their investigation suggests that many of the distant peculiar galaxies evolve to become today’s spiral galaxies through gas-rich galactic collisions — a conclusion that is at odds with the belief that galaxy collisions lead to the formation of ellipticals. Such evidence needs to be taken into account in testing theories of galaxy formation and evolution. Ana Lopes NASA/ESA/SDSS/F. HAMMER & R. DELGADO-SERRANO (OBS. PARIS) A, D. SIVETER/REF. 2; B, J. CHEN NEWS & VIEWS NEWS & VIEWS NATURE|Vol 463|11 February 2010 early vertebrates? Or is it a more pervasive phenomenon? In general, the answer is that stem-ward slippage is widespread: all fossil animals with a high proportion of missing information tend to fall out near the base of an evolutionary tree through the lack of morphological features (such as structures in the head, in the case of chordates) to ally them with more evolved groups. And the resulting tree may be biased unless the decay sequence is random relative to the tree’s branching order — that is, the order in which characters evolved. As well as prompting caution in interpreting soft-bodied fossils, Sansom and colleagues’ research1 may turn out to be important in identifying a way to assign confidence limits to the placement of these extinct forms in the tree of life. ■ Derek E. G. Briggs is in the Department of Geology and Geophysics, and the Yale Peabody Museum of Natural History, Yale University, New Haven, Connecticut 06520, USA. e-mail: [email protected] 1. Sansom, R. S., Gabbott, S. E. & Purnell, M. A. Nature 463, 797–800 (2010). 2. Hou, X.-G. et al. The Cambrian Fossils of Chengjiang, China: The Flowering of Early Animal Life (Blackwell, 2004). 3. Caron, J.-B. & Rudkin, D. (eds) A Burgess Shale Primer: History, Geology, and Research Highlights (Burgess Shale Consortium, 2009). 4. Briggs, D. E. G. Annu. Rev. Earth Planet. Sci. 31, 275–301 (2003). 5. Gabbott, S. E., Hou, X., Norry, M. J. & Siveter, D. J. Geology 32, 901–904 (2004). 6. Donoghue, P. C. J. & Purnell, M. A. BioEssays 31, 178–189 (2009). 7. Schäfer, W. Ecology and Palaeoecology of Marine Environments (Chicago Univ. Press, 1972). a No benzodiazepines Glutamatergic neurons B1-containing GABAA receptor Glutamate receptor Dopaminergic neurons Interneurons Inhibition Low activity b Benzodiazepines bound Glutamatergic neurons NEUROSCIENCE Lack of inhibition leads to abuse Strengthened synapse Benzodiazepine Arthur C. Riegel and Peter W. Kalivas Chronic drug use can lead to addiction, which is initiated by specific brain circuits. The mystery of how one class of drugs, the benzodiazepines, affects activity in this circuitry has finally been solved. Common illnesses such as anxiety disorders, insomnia and even muscle spasms are treated with benzodiazepine drugs, of which diazepam (Valium) is perhaps the best known. But both conventional benzodiazepines and newer benzo diazepine-like compounds (such as zolpidem) are addictive. This limits the therapeutic potential of an otherwise safe class of drugs that has broad clinical applications. Most addictive substances activate the same brain circuitry: the dopaminergic system, which is also stimulated by natural rewards, such as food and sex. Benzodiazepines stimulate this circuitry, but the underlying mechanism was unknown, prompting speculation that benzodiazepine addiction involves systems distinct from those involved in dependence on other addictive drugs. In this issue (page 769), Tan et al.1 report that the missing link connecting benzodiazepines to the dopaminergic circuitry is a select group of GABAA receptors (γ-aminobutyric acid type A receptors) that reside on neurons known as inhibitory interneurons. These interneurons coordinate the output of dopaminergic neurons in the ventral tegmental area (VTA) of the brain. GABAA receptors are assembled from five subunits, of which there are several types; the authors find that, in inhibitory interneurons, benzodiazepines increase the stimulation of GABA A receptors that contain α1 subunits. This reduces activity in the interneurons and thereby increases excitability in VTA dopaminergic cells. Through a series of ingenious experiments, Tan et al. demonstrate that this mechanism contributes to benzodiazepine addiction. In general, the urge to self-administer an addictive drug is initiated in the VTA by the ‘strengthening’ of excitatory glutamatergic synapses — neural junctions at which glutamate is the primary neurotransmitter — to dopaminergic neurons. Such strengthening increases the chance that the synapse will release glutamate and is caused by the recruitment of new AMPA receptors (a class of glutamate receptor) to glutamatergic synapses on dopaminergic neurons. In agreement with an earlier study2, Tan et al.1 found that benzodiazepines also cause this effect in mice, regardless of whether the drugs are injected systemically (whereupon they can interact with GABAA receptors throughout the animal’s body) or directly infused into the VTA. The authors obtained similar results with zolpidem, which binds predominantly to GABAA receptors that contain α1 subunits. But they detected no such strengthening in wildtype mice in which a benzodiazepine was coadministered with a compound that blocks the benzodiazepine binding site on GABAA receptors (a benzodiazepine antagonist), or in mice that were genetically engineered so that their α1 subunits were unable to bind benzodiazepines. Taken together, these results showed that the cellular changes that occur in dopaminergic neurons after a single exposure to benzodiazepines require functional α1 subunits in GABAA receptors. Tan et al. then mapped the location of © 2010 Macmillan Publishers Limited. All rights reserved Interneurons Disinhibition Dopaminergic neurons Increased activity Figure 1 | Proposed mechanism of addiction of benzodiazepine drugs. Tan et al.1 report that benzodiazepine drugs bind to and activate certain GABAA receptors (γ-aminobutyric acid type A receptors) — those that contain α1 subunits — on interneuron cells in the ventral tegmental area (VTA) of the brain. a, These interneurons ordinarily inhibit the activity of dopaminergic neurons in the VTA. Forked branches are synapses (neural junctions). b, Activation of the GABAA receptors by benzodiazepines reduces the amount of inhibition (a process known as disinhibition, red cross), which increases the activity of the VTA’s dopaminergic neurons. This increased activity strengthens the VTA’s glutamatergic synapses (neuronal junctions at which the primary neurotransmitter is glutamate) to dopaminergic neurons, making them more excitable. Such strengthening, caused by an increase in the number of glutamate receptors on the dopaminergic neuron, is the cellular response to natural rewards (such as food), but it also forms the basis of the addictive properties of drugs. α1-containing GABAA receptors within the VTA’s microcircuitry, and found that the highest density was not on dopaminergic cells, but on the inhibitory interneurons — the same class of cells targeted by opioid drugs such as morphine3. In fact, much of morphine’s addictive potential is attributed to the inhibition of these interneurons in the VTA. To better understand commonalities between benzodiazepines and opioids, the authors 1 treated α1-mutated mice with morphine. Surprisingly, they observed that morphine caused the cellular changes 743