news and views plasmic reticulum cisternae — a process that dynamics seem to have ancient origins. or anionic species similar to the group-6 involves an unknown AAA-type ATPase11. Archaebacteria — cells that lack internal elements, but not cationic species like Even more intriguing is the identity of the membranes — contain a homologue for uranium. There is no guarantee that other membrane-bound p97/p47 receptors. Are p97, suggesting an ancestral role in the chemical species containing seaborgium they related to the SNARE proteins that are fusion events that accompany cell division. won’t have more peculiar chemistry — the involved in Rab-dependent NSF/SNAP- Many members of the family could have relativistic effects may be different for differ- mediated membrane recognition? If so, evolved with the emergence of compartmen- ent molecular orbitals — but for now the AAA-type ATPases may be central to prim- talized cells. They may use a subset of struc- periodic table is firm. ing the assembly of different membrane- turally and functionally related accessory The practicalities of chemistry on these targeting protein complexes. proteins, and a common molecular mecha- elements are daunting. Chemists have to work Why does the cell use distinct, but related, nism, to promote membrane recognition. with short-lived radionuclides and very low AAA-type ATPases in membrane dynamics? But for now, the identification of the production rates, so experiments must be Both NSF and p97 are necessary for reassem- p97/p47 complex by Kondo et al.6 represents performed quickly and still efficiently sepa- bly of the Golgi apparatus — NSF seems to an important step towards working out the rate the desired nuclide from similar prod- mediate the initial heterotypic recognition general principles of how the AAA-type ucts. Any chemistry that depends on com- of small vesicles, whereas p97 promotes the ATPases act. plexes containing two or more of the studied subsequent homotypic-recognition events Tony Rowe and William E. Balch are in the atoms must be avoided, because of the one- that lead to the formation of cisternae4,5. Department of Cell Biology, The Scripps Research atom-at-a-time nature of these experiments Moreover, two AAA-type ATPases (the PAS1 Institute, 10550 North Torrey Pines Road, La Jolla, — just three daughter decay chains were and PAS5 gene products2) are required for California 93037, USA. observed in 5,000 solution-chemistry experi- peroxisome biogenesis in yeast. So the main- 1. Rothman, J. E. Nature 372, 55–63 (1994). ments on seaborgium, for example — and tenance of subcellular compartments may, in 2. Confalonieri, F. & Duguet, M. BioEssays 17, 639–650 (1995). direct measurement of the large number of general, involve both homotypic and hetero- 3. Latterich, M., Frohlich, K.-U. & Frohlich, R. S. Cell 82, 885–893 atoms needed to measure physical properties (1995). typic membrane recognition and fusion 4. Rabouille, C., Misteli, T., Watson, R. & Warren, G. J. Cell Biol. is impossible. Even though the chemistry of events, which probably require the activity of 129, 605–618 (1995). single atoms should be identical to that of a diverse AAA-type ATPases (Fig. 1). Given the 5. Acharya, U. et al. Cell 82, 895–904 (1995). large number, additional experiments with importance of p97 in the reassembly of the 6. Kondo, H. et al. Nature 388, 75–78 (1997). radioactive tracers are usually made to con- 7. Morgan, A. & Burgoyne, R. D. Trends Cell Biol. 5, 335–339 (1995). Golgi stack during mitosis, it will be interest- 8. Nichols, B. J., Ungermann, C., Pelham, H. R. B., Wickner, T. & firm this expectation. Finally, materials or ing to see whether it, and possibly other, Haas, A. Nature 387, 199–202 (1997). chemicals that act as trapping agents, as many members of the AAA-type ATPase family are 9. Haas, A., Scheglmann, D., Lazar, T., Gallwitz, D. & Wickner, W. precipitates do, must usually be avoided. (An regulated in a cell-cycle-dependent manner. EMBO J. 14, 5258–5270 (1995). exception is the clever chemistry4 that showed 10.Rybin, V. et al. Nature 383, 266–269 (1996). The members of the AAA-type family 11.Turner, M. D., Plutner, H. & Balch, W. E. J. Biol. Chem. 272, the group-5 element hahnium to be like of ATPases that are involved in membrane 13479–13483 (1997). niobium and protactinium, by its absorption on glass from solution in nitric acid.) Chemistry The short-lived man-made elements are produced by charged-particle accelerators, Oddly ordinary seaborgium instead of the classical techniques that separate elements from natural materials, Ron Lougheed nuclear-explosion debris or reactor materials. The particle beam is aimed at a thin target, he correct position of new elements screens the nucleus electrostatically from from which the reaction products emerge in the periodic table is not a trivial other electrons with higher angular momen- at high speed. They are then usually trans- Tmatter. We understand the periodic tum, whose orbits consequently expand. ported in a gas jet to the chemical apparatus table in terms of the filling of electron shells — Relativistic effects can even be important in seconds, and separated by gas or liquid a process that would seem to be entirely pre- in lighter elements — for example, they chromatography, or solvent extraction. dictable. But relativistic effects can make the explain the stability of the +1 oxidation state The subsequent decay, usually by Ȋ- heaviest elements, notably rutherfordium in thallium — but because these effects particle emission or spontaneous fission, is and hahnium1, behave in unexpected ways. increase as the square of the nuclear charge, 1234567 Now, working with just seven atoms, Schädel the greatest effect is expected in the heaviest 2 et al. on page 55 of this issue have extended elements. It isn’t easy to predict what Rb Sr Y Zr Nb Mo Tc chemistry to element 106 (seaborgium). They will happen, though: the heaviest-known 37 38 39 40 41 42 43 place it firmly in group 6, under tungsten and group-5 element hahnium behaves more like Cs Ba La Hf Ta W Re molybdenum (Fig. 1), raising the question of the actinide protactinium and the lighter 55 56 57 72 73 74 75 why it behaves in such a conventional way. group-5 element niobium than its closest Fr Ra Ac Rf Ha Sg Ns In this region, from the actinides on, one homologue tantalum3; so tantalum could be 87 88 89 104 105 106 107 cannot predict properties by simple extrapo- considered the oddest member of group 5. Actinides Th Pa lation of the periodic table. The high charges If seaborgium is a conventional group-6 90 on these large atomic nuclei mean that the element, its properties will be similar to 91 U 92 Np electrons are tightly bound, orbiting at rela- those of tungsten or molybdenum, its lighter 93 tivistic velocities (a substantial fraction of the homologues; and it could also have some speed of light). And in many cases valence properties similar to those of uranium. Lanthanides electron levels are close, and their order Schädel and colleagues have shown by gas Ce Pr Nd Pm can be swapped by relatively small effects. chromatography that seaborgium forms 58 59 60 61 Electrons with low angular momentum (in volatile oxyhalides similar to the group-6 Figure 1 Part of the periodic table, including the 2 the s and p1/2 shells) overlap the nucleus elements , and by liquid chromatography early actinides, and the three latest elements to strongly enough to be drawn into tighter experiments, using nitric acid and dilute have their chemistry analysed: rutherfordium orbits, partly by relativistic effects. That hydrofluoric acid, that it forms neutral (104); hahnium (105); and now seaborgium (106).

NATURE | VOL 388 | 3 JULY 1997 21 news and views measured, to determine which chemical that chemical studies will extend beyond one responses with behavioural measurements fraction contains the atoms (for example, in or two more elements. Yet new nuclides with obtained for the same stimuli and observers, the liquid chromatography experiments, half-lives long enough for chemical studies they have found that the activity of the whether the atoms come through the col- are predicted, at least up to element 114. red–green and blue–yellow colour-opponent umn or stick to it). These experiments have Only a few atoms of these nuclides might be mechanisms seems to underlie both sets of evolved from a few to several hundred manu- produced in months of bombardment. data. al operations, with the gradual addition of Intense radioactive beams using neutron- Less than ten years ago, in a survey of automation to increase both speed and rich projectiles are one possible route to neuroscientific methods, Churchland and reliability, until, in the very advanced minia- increased production, still far in the future Sejnowski4 exposed a gaping hole in the ture automated chemistry described in the — but perhaps not so far, when we note that research — namely, that no method existed present paper, even the chromatographic the first chemistry of seaborgium has come to study the activity of large ensembles of columns are changed automatically, and 23 years after its discovery. neurons, or even whole cortical areas, over a several thousand experiments are repeated. Ron Lougheed is in the Lawrence Livermore time course of several seconds. The sub- To what elements can chemistry be National Laboratory, University of California, sequent advances in imaging techniques, and extended? Older predictions were that chem- Livermore, California 94550, USA. especially the availability of fMRI (ref. 5), ical experiments would end in the heavy 1. Schädel, M. Radiochim. Acta 70, 207–223 (1995). promised the missing link (Fig. 2). 2. Schädel, M. et al. Nature 388, 55–57 (1997). actinides. Using present-day production 3. Kratz, J. V. et al. Radiochim. Acta 48, 121–133 (1989). Functional MRI is based on blood- methods and available targets, it is not likely 4. Gregorich, K. E. et al. Radiochim. Acta 43, 223–231 (1988). oxygen-level-dependent (bold) changes in the magnetic resonance signal. The bold Visual neurobiology assumption is that the blood oxygen level is an indicator for local cortical activity. Colouring the cortex Because there is activity everywhere — even in the resting brain — only the activity Karl R. Gegenfurtner changes that are induced by stimuli differing in the attribute of interest are measured. The n humans, the neural basis for colour single-cell recordings in the next stage, the resulting difference in the fMRI signal is typi- vision lies in the activity of the ‘colour- primary visual cortex (V1), where neurons cally about five per cent of the total signal, opponent’ neurons, which receive inputs that add inputs from all three cone types and it depends on the stimulus that is used. I 2 of opposite sign from the three different predominate . For example, if a region responds differen- classes of cone photoreceptors that are found On page 68 of this issue, Engel et al.3 tially to a moving stimulus, it is tagged as the in the eye (Fig. 1). Colour-opponent neu- report that, in sharp contrast to the single- ‘motion centre’ in the brain. Several such rons are abundant in the first stages of the cell recordings, most of the activity that is processing centres have been found, and visual pathway — the retina and the lateral detected by functional magnetic resonance the trend is going towards a ‘grandmother geniculate nucleus1. Surprisingly, however, imaging (fMRI) of visual cortical areas V1 centre’. This is analogous to the trend towards they are observed rather infrequently by and V2 in humans is due to the activity increasingly specialized processing units6, Retinal ganglion of colour-opponent cells. Until now, most which came about from single-cell record- Cone cells fMRI studies have only shown that there is a ings during the 1970s. Clearly, it is implicitly photoreceptors LGN cells change in activity in a defined brain region assumed that information processing is

1 M when a particular stimulus is used. But Engel managed by specialized brain regions — S L et al. have measured differential responses to distributed processing goes unnoticed in L+M subtle changes in colour and contrast, so the this standard approach. 0.1 7,8 ‘luminance’ levels of activity in the fMRI signal can be More recently, several groups have

Sensitivity used to produce response contours for the developed strategies to distinguish between 0.01 whole range of colours. By comparing these visual cortical areas by exploiting the system-

400 500 600 700 L-M Wavelength (nm) ‘red–green’ 3 Evoked Psychophysics potentials Brain 2 fMRI PET 1 Optical Lesions Column S-(L+M) 0 dyes ‘blue–yellow’ –1 Figure 1 In human colour vision, the Neuron Single unit information from the three different types of –2 Patch clamp Light microscopy cone photoreceptors, short-, middle- and long- –3 Synapse wavelength-sensitive (S, M, L), is combined by (log mm) Spatial resolution –4 retinal ganglion cells and cells in the lateral geniculate nucleus (LGN) into two chromatic -3 -2 -1 0 1 2 3 4 5 6 7 channels and a luminance channel1. The spectral Millisecond Second Minute Hour Day sensitivities of the cone photoreceptors are Temporal resolution (log s) shown to the left. Chromatic channels receive Figure 2 Spatial and temporal resolution of some of the most common experimental methods that are signals of opposite sign from the cones. These used to study sensory processing. Green boxes indicate non-invasive methods; red boxes indicate opponent channels are often labelled ‘red–green’ invasive methods. The blue shaded area indicates a time slice of major interest, between 100 ms and and ‘blue–yellow’, even though the stimuli that 10 s. Engel et al.3 used functional magnetic resonance imaging (fMRI) to show that most of the differentially activate them (shown to the right) activity in the visual cortical areas V1 and V2 in humans is due to the activity of colour-opponent appear to be a noticeably different colour11. cells. The precise resolution of fMRI is often overestimated — even though images can be acquired Increasing contrast results in the appearance of every 50 ms with an accuracy of 1 mm, the underlying changes in blood oxygen level are much slower more saturated colours. and coarser12. PET, positron emission tomography. (Modified from ref. 4.)

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