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reverse transcription mechanism, primed by 2. Jacquier, A. Trends Biochem. Sci. 15, 351-354 (1990).
wires attached at each corner. One of these target DNA, that is similar to group II retro- 3. Michel, F. & Ferat, J. Annu. Rev. Biochem. 64, 435-461 (1995).
possible modes is shown in colour. Because 4. Eskes, R., Yang, J., Lambowitz, A. M. & Perlman, P. S. Cell 88,
only specific modes are allowed, the phonon spectrum is quantized in these nanobridges.
5. Matsuura, M. et al. Genes Dev. 11, 2910-2924 (1997).
Thomas H. Eickbush is in the Department of 6. Cousineau, B. et al. Cell 94, 451-462 (1998).
Similarly, oscillations in the wires of the Biology, University of Rochester, Rochester, New 7. Mohr, G., Smith, D., Belfort, M. & Lambowitz, A. M. Genes nanoharp (Fig. 1a) can occur only at a par- Dev. 14, 559-573 (2000).
ticular set of discrete frequencies, much as 8. Sharp, P. A. Cell 42, 397-400 (1985).
the strings in a full-sized harp are restricted 9. Cech, T. R. Int. Rev. Cytol. 93, 3-22 (1985).
1. Cousineau, B., Lawrence, S., Smith, D. & Belfort, M. Nature 10. Yang, J., Malik, H. & Eickbush, T. H. Proc. Natl Acad. Sci. USA to resonate at certain frequencies. In the 404, 1018-1021 (2000).
96, 7847-7852 (1999).
nanoharp, these frequencies form the quan-tized spectrum of allowed wavelengths.
Nanotechnology
affect the flow of heat? Dimensionality playsan important role here. Each nanobridgeshown in Fig. 1a is a one-dimensional (1D) Heat flow through nanobridges
system, in which phonons are free to move Leo P. Kouwenhoven and Liesbeth C. Venema only in the longitudinal direction. In general,1D systems display many quantized trans-port phenomena, irrespective of what is Schwab et al.1, various phonons are gener- ated by heating (Fig. 1b). But only specific other carriers)2. For instance, the flow of one side, energy will flow to the coldend. In solid material, heat can be atoms vibrating around their fixed, equilib- quantized conductance in units of 2e2/h rium positions. Insulating materials do not (where h is the Planck constant and e is the charge on an electron). In other words, each vibrations can transport heat in insulators.
mode of electrical transport contributes a These vibrations are not random: the atoms maximum value (independent of the materi- move collectively so that together they form al involved) of 2e2/h to the conductance.
waves, called phonons. Objects in everyday life, such as a ceramic cooking pot, contain turned out to be a very general phenomenon.
many different types of phonons with vary- It was first discovered in sub-micrometre- ing wavelengths, which carry heat from the scale semiconductor transistors3,4. Later, hot to the cold end. But by making objects smaller and smaller, today's trend in physics systems of two metals connected by a single emerge that are not evident in large materi- als. On page 974 of this issue, Schwab et al.1 solution6. Besides electrons, analogous 1D report an experiment involving an extremely observed for photons, for pairs of electrons nons. A nanometre is a billionth of a metre, in superconductors, and for heat carried by making the bridges about 500 atoms wide.
The authors find that the amount of heat that can flow across the nanobridge is bound by similar quantized behaviour. This may seem an upper limit, set by the laws of quantum transports charge and mass, whereas a heat In the world of nanoscale objects, such as the nanoharp shown in Fig. 1a, heat cannot obey different quantum statistics. Nonethe- length. Of all possible phonons, the one with less, one single formula describes it all: the the longest wavelength that just fits within the material has the lowest energy. Longer Figure 1 The nanoscale world. a, Parallel
reservoirs and is applicable to both electrons nons) are not allowed. For smaller objects, nanobridges forming a nanoharp. The sound in
the bridges of the nanoharp is restricted to
certain resonant frequencies, as in a full-sized
larity, the experimental requirements are increases. When the object is so small that harp. Both sound and heat are carried through
hugely different. Commercial batteries and solids by phonons. The word phonon refers to
ampere meters are sufficiently sensitive to thermal energy, k T (where k is the Boltz- the Greek word 'phon' for sound. (Photo
measure quantized electrical conductance.
mann constant and T the temperature), courtesy of H. G. Craighead, Cornell
(Note that (2e2/h)ǁ1 is equal to 13 kȉ, and is University.) b, In the device created by Schwab
therefore an easy resistance to measure.) In et al.1, phonons are generated in the central
contrast, for the observation of quantized square by thermal heating. Some of these
wavelengths and characters can exist. Each phonons can leave this region by way of the four
voirs, various technical difficulties have to be leads to a specific mode of wave-like motion suspended nanobridges. The colours indicate
solved. First, to achieve good thermal isola- in an object, such as twisting or bending in the local strain amplitude. (Simulation by D.
a wire. In the centre of the device created by Harrington, Caltech.)
freely suspended (Fig. 1a). This is not an easy NATURE | VOL 404 | 27 APRIL 2000 | www.nature.com 2000 Macmillan Magazines Ltd
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task on the scale of a hundred nanometres. the striatum)4 and the deposition of polyglu- In addition, a sensitive technique is needed phonons is saturation of the thermal con- tamine aggregates both within and outside to heat one end of the wire and measure ductance at very low temperatures, precisely nuclei (primarily in neurons of the brain's the temperature difference between the two at the quantum value Ț2k 2T/3h. cortex)5,6. The precise relationship between ends with millikelvin resolution. Schwab This observation by Schwab et al. is the the aggregation process and the malfunction et al.1 have managed to construct such a first demonstration of quantum physics in and death of nerve cells is uncertain.
measurements at ultra-low-power levels.
express exon 1 of the HD gene with long They find that a single phonon mode can at counting, double-slit interference experi- most contribute a quantum of Ț2k 2T/3h to ments with single phonons, and many many features reminiscent of Huntington's disease7. In this model, a late-onset, progres- sively worsening movement disorder is pre- transport, a sequence of conductance steps is Leo P. Kouwenhoven and Liesbeth C. Venema are in ceded by the formation of the characteristic observed as the electronic states fill up. With the Department of Applied Physics, Delft University phonons, in contrast, the authors find a sin- of Technology, PO Box 5046, 2600 GA Delft, The time that symptoms appear, the binding of a gle plateau at low temperatures, which then particular neurotransmitter (dopamine) to rises linearly with temperature at higher temperatures. The reason is that electronic as do levels of the messenger RNA encoding states are either full or empty - the change 1. Schwab, K., Henriksen, E. A., Worlock, J. M. & Roukes, M. L.
that receptor10. The brains of Huntington's in occupation occurs in a sharp, discontinu- Nature 404, 974-977 (2000).
ous step. The occupation of phonon states 2. Van Houten, H. & Beenakker, C. W. J. Phys. Today 22-27 July Yamamoto et al.1 have built on this work, is actually regulated by the temperature (as 3. Van Wees, B. J. et al. Phys. Rev. Lett. 60, 848-850 (1988).
taking advantage of a conditional regulato- 4. Wharam, D. A. et al. J. Phys. C 21, 209-214 (1988).
ry system12 that allows the mutant exon 1 Ț2k 2T/3h on T). When the temperature is 5. Muller, C. J., van Ruitenbeek, J. M. & de Jongh, L. J. Phys. Rev. HD gene to be switched on or off. They Lett. 69, 140-143 (1992).
found that, when the gene was switched on 6. Frank, S. et al. Science 280, 1744-1746 (1998).
occupied. But instead of a series of steps, 7. Imry, Y. & Landauer, R. Rev. Mod. Phys. 71, S306-S312 (1999).
in mice, it was expressed throughout theanimals' lifetime. The mice developed aprogressive neurological phenotype: onset Huntington's disease
of a motor disorder was seen at 4 weeks ofage; a mild tremor was present by 20 weeks;and mice were clearly underactive by 36 In reverse gear
weeks. Yamamoto et al. detected nuclear staining specific to the mutant HD gene, aswell as intranuclear and extranuclear polyg-lutamine aggregates, in brain sections of polyglutamine tract of varying length. When mice at 8 weeks. The brains of the mice were the tract is 38 glutamines long or more, the smaller than normal, with a marked reduc- Cell, describe a mouse model of Hunt-ington's disease with a difference: the protein gains toxic properties. On autopsy, tion in the size of the striatum. A reduction pathological features and symptoms of the the brains of Huntington's patients show a in binding of dopamine to its receptors was disease can be reversed. These findings are selective death of neuronal cells (mainly in also seen. This is all in line with what would both dramatic and unexpected, and indicate- with the obvious caveat that we do not yet humans - that it may be possible to treat Huntington's disease is an inherited, late- onset neurodegenerative disease for whichthere is no known cure. In the Western worldit affects about 1 in 10,000 people, with aslightly larger number than this being at riskof developing the disease. Symptoms include changes in personality, cognitive decline and a movement disorder (such as uncontrol-lable, jerky movements, called chorea)2.
Patients suffering from Huntington's dis- ease bear alterations in the HD gene3. Closeto the beginning of this gene - in a protein-coding part, exon 1 - is a region that includes a variable number of a trinucleotide motif (the cytosine/adenine/guanine, orCAG, motif). The only difference between Figure 1 Progression and reversal of Huntington's disease in a mouse model. Red lines represent the
the HD gene in unaffected and affected indi- relative progression of the various characteristics of Yamamoto et al.'s mutant mice1 over a 34-week
viduals is the number of copies of this motif.
period. In one set of mice, the mutant gene was turned off at 18 weeks of age by adding the antibiotic
doxycycline to the animals' drinking water. The blue lines represent the degree to which each of the
acid glutamine, and so the huntingtin pro- characteristics shown was either halted or reversed when the gene was no longer expressed.
tein encoded by the HD gene contains a Dopamine is a neurotransmitter; reactive glial cells are generally indicative of nerve cell loss.
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