Vision is the richest of the human senses, and detectors of light havelong featured in science and technol-

ogy. In fields as diverse as telecommunica-tions, medicine and astronomy, there isdemand for exquisitely sensitive detectors ofthe quantum of light, the photon. But as yetthere is no single commercial device that can simultaneously detect individual visiblephotons and record the colour (or energy)and arrival time of each photon. If such adetector existed, it should also produceimages with many picture elements (pixels)— and be affordable. Day and colleagues1

now propose a device, based on the prin-ciple of kinetic inductance, that could function as an individual pixel in a photondetector (page 817 of this issue). Importantly,they show that the device has the necessaryproperties to allow the incorporation of

many such pixels into the ‘ultimate’ photondetector, one that could also be read outwith practical, available electronics.

The search for the ultimate photon detec-tor has been driven by astronomers, who areoften faced with a limited number of pho-tons to measure,emitted from some object inour Galaxy or beyond, and limited time inwhich to measure them. At present, astron-omy is well served by the charge-coupleddetector (CCD), familiar to many people asthe CCD sensor in their digital camera orcamcorder. Megapixel CCDs are now com-mon. But this detector cannot resolve indi-vidual photons, because the noise occurringrandomly in its readout electronics is toolarge to allow it. Moreover, the physics ofthe detector precludes the measurement ofphoton colour, unless colour filters are used.These reduce efficiency, but without such

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filters a CCD would see only shades of grey.To record single photons cleanly and to

discern their energy and arrival time requiresa detector that operates at low temperatures.This gets rid of the thermal agitation in thedevice that would disrupt a single-photonsignal, and also means that materials andtechniques can be used that are fundamen-tally different from those employed in theCCD.The first advance in cryogenic detectortechnology was the silicon ‘microbolo-meter’2, in which a small piece of silicon isheld at 0.05 K but heats up when a photon isabsorbed. The subsequent rise and fall ofthe temperature is recorded, to determinethe photon energy. These detectors areemployed by astronomers for rocket-basedobservations of photons at X-ray wave-lengths, with an energy 100 to 1,000 timesthat of visible photons.But their sensitivity isnot sufficient to record visible photons, withan energy of 1.5 to 3 electronvolts.

Over the past decade, new devices havebeen developed that are more sensitive andcan record visible photons3–9.These detectorsfall into two classes.The first is the bolometer,which uses the same heating effect as mentioned above to determine photon ener-gy. The thermometer inside such a device,recording the temperature change, is a strip

Applied physics

To catch a photonDaniel E. Prober

Astronomers crave a detector sensitive enough to detect a singlephoton and determine its energy. A new single-pixel device can do this,and could also be built up into a large array suitable for a telescope.

Gregor Mendel’s remarkable studiesof peas revealed a straightforwardpattern of genetic inheritance. Butsince then we’ve learned thatmatters are not always so simple:many identifiable traits result fromcomplex interactions betweenmultiple genes and environmentalfactors. Current work in geneticsaims to quantify the contributions ofspecific variations in each gene tothe mix. But pinpointing the rightspot in an animal’s huge genomecan be a nightmare, even inorganisms that have had theirgenome completely sequenced.

The humble pig, meanwhile,has only recently received its owngenetic map — a first-generationsketch of what its genome sequencemight look like. Imagine, then, howdifficult it must have been to findone specific nucleotide that controls15–30% of the variation in musclemass seen between pigs. But that’sjust what Anne-Sophie Van Laere et al. report elsewhere in this issue(Nature 425, 832–836; 2003).

The authors find that a changefrom a guanine nucleotide to anadenine at a specific point in the

IGF2 gene can add 3–4% moremeat to a pig. The nucleotidechange disrupts the regulation ofIGF2, increasing its expressionthreefold in muscle but not at all in liver, another main organ ofexpression. As the IGF-II proteinstimulates muscle growth, the resultis a pig with more muscle and lessfat — a boon for meat production.And, as the change occurs in part

of the gene that does not actuallycode for protein, it suggests thatresearchers should not study justthe protein-coding bits when lookingfor important genetic differencesbetween individuals.

Of course, farmers don’t need to know the exact mechanisminvolved; they spotted this physicaltrait years ago and selected for it inbreeding schemes. Thus, Van Laere

et al. show that the muscle-favouring alteration has sweptthrough commercial pig populations,but is not present in Asian orEuropean wild boars tested. Nowthat the pig is lining up with otherfarm animals such as cows andchickens to have its genomesequenced, we should be able tofind other genetic contributions tobulked-up pigs. Chris Gunter

Genetics

Secrets of a porkier porker

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size of the osteoblast population in specificregions of bone. They then looked at how this affected the HSC population. In essence,they found that increasing the number ofosteoblasts causes parallel increases in theHSC population.

Zhang et al.7 looked at the involvement ofsignalling by bone morphogenetic protein(BMP) in HSC regulation. The activity ofBMP is crucial to the development of blood-forming tissue in embryos. The authorsshow that mutant mice depleted of a cellularreceptor for BMP develop bone abnormali-ties — calcified ‘trabecular bone-like areas’form within long bones.And the numbers ofprimitive long-term (LT) HSCs are approxi-mately doubled in these animals. Theauthors go to considerable lengths to dem-onstrate that the HSC pool is specificallyincreased without concomitant increases inother primitive progenitor cell populations.Such a specific increase in only the LT-HSCpopulation is consistent with very localeffects; in other words, it suggests that a veryspecific niche is functionally enhanced.

To gain further insight, the authorsemployed a more elaborate genetic strategyin which a fluorescent green protein markerwas activated in cells that were depleted ofthe BMP receptor. Only the osteoblasts thatlined the surface of the bone-like area fluor-esced.Using a combination of cell markers tolabel the LT-HSCs, Zhang et al. found thatthe stem cells co-localized with spindle-shaped osteoblasts lining the bone surface.And a doubling of this osteoblast populationmirrored the increase in the LT-HSC popula-tion in the mutant mice. These osteoblasts,and a subpopulation of the HSCs, expressed N-cadherin, a cell-surface molecule thathelps cells adhere to one another. Theauthors suggest that N-cadherin and a pro-tein that forms a complex with it, b-catenin,might form important components of theinteraction between the stem cell and itsniche. To prove this, it will be necessary to

of partly superconducting metal3,6; the read-out amplifier is also superconducting.As superconductivity — the flow of currentwithout resistance — is a low-temperatureproperty, the entire structure of the device is a cryogenic environment (which is easier toengineer than a device with only some super-conducting components).

The second class of detector makes use ofthe electron excitations created in solids bythe energy of an incoming photon5. Numer-ous observations have been made with suchdetectors developed at the European SpaceAgency7–9,including observations of the Crabnebula and short-period binary systems,known as polars9. The readout electronics ofthese detectors, however, operates at roomtemperature, with the consequence that thenumber of channels that can be read out islimited. So far, the number of pixels in animage has been limited to 36. Clever devicedesign might mean that this number of pixelscan be expanded by a factor of maybe 10 to 20,but the engineering is proving difficult.

Day et al.1 now present a new approach to the problem of photon detection. Theirdevice contains a superconducting film held at low temperature. Inside the film,resistanceless current flows in the form ofelectron pairs. If a photon hits the device, itcan break up some of these pairs, with theresult that the supercurrent becomes more‘sluggish’10. That increase in sluggishness can be detected in the surrounding micro-wave circuitry. The nature of the measure-ment is akin to watching an object on aspring, vibrating at the natural oscillationrate: the rate of the spring’s vibration revealsthe mass (‘sluggishness’) of the object.

The authors also show that cryogenic elec-tronics systems already available are adequatefor the readout of the signal from their device.Device and readout together make the desired single-photon detector. Moreover,the method of readout used can be rather easily generalized to accommodate hundreds,and perhaps thousands,of pixels.Other fieldsof science, such as fluorescence microscopystudies of single molecules, should also ben-efit from this new detector technology.

The ultimate photon detector, however,is not yet at hand. Some challenges remainfor Day and colleagues’design1: for example,although there is very little noise in the read-out system, the detector itself has not yetachieved that low level of noise. Whether thenoise source is intrinsic or extrinsic is notclear, but I am optimistic that it can be rem-edied. Meanwhile, in the race to produce theultimate photon detector, the other candi-dates (mentioned above) are advancing11–13.The winner — or winners — of this race willbe determined in part by issues that gobeyond performance,such as cost and ease ofuse. Practical engineering factors hold swayin astronomy, just as in regular life. ■

Daniel E. Prober is in the Departments of Applied

Physics and Physics, Yale University, New Haven,Connecticut 06520-8284, USA.e-mail: daniel.prober@yale.edu

1. Day, P. K., LeDuc, H. G., Mazin, B. A., Vayonakis, A. &

Zmuidzinas, J. Nature 425, 817–821 (2003).

2. Moseley, S. H., Mather, J. C. & McCammon, D. J. Appl. Phys. 56,

1257–1262 (1984).

3. Stahle, C. K., McCammon, D. & Irwin, K. D. Phys. Today 52,

32–37 (1999).

4. Mather, J. C. Nature 401, 654–655 (1999).

5. Twerenbold, D. Rep. Prog. Phys. 59, 349–426 (1996).

6. Cabrera, B. et al. Appl. Phys. Lett. 73, 735–737 (1998).

7. Peacock, A. et al. Nature 381, 135–137 (1996).

8. Nadis, S. Science 274, 36–38 (1996).

9. Verhoeve, P. AIP Proc. Conf. 605 (1), 559–564 (2002).

10. VanDuzer, T. & Turner, C. W. Principles of Superconductive Devices

and Circuits (Prentice Hall, Englewood Cliffs, New Jersey, 1999).

11. Cabrera, B. et al. AIP Proc. Conf. 605 (1), 565–570 (2002).

12. Stevenson, T. R., Pellerano, F. A., Stahle, C. M., Aidala, K. &

Schoelkopf, R. J. Appl. Phys. Lett. 80, 3012–3014 (2002).

13. Schoelkopf, R. J. et al. Science 280, 1238–1242 (1998).

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Stem cells

Interactive nichesIhor R. Lemischka and Kateri A. Moore

The microenvironment, or niche, in which stem cells reside controlstheir renewal and maturation. The niche that regulates blood-formingstem cells in adult animals has eluded researchers — until now.

Cell-fate decisions in the developingembryo are governed by a complexinterplay between cell-autonomous

signals and stimuli from the surrounding tissue — the microenvironment. Similarprocesses control the birth and maturationof stem cells that replenish mature cell popu-lations in adults1,2. But where are the stem-cell microenvironments located in adulttissues? And what other cell types contributeto these ‘niches’? In mammals, the niches forgut and certain skin stem cells have beenpinpointed, and in several cases the molecu-lar signals that emanate from them havebeen identified3–6. Somewhat ironically, how-ever, the niches that interact with the best-characterized mammalian stem cells, thehaematopoietic stem cells (HSCs), whichreplenish at least ten blood-cell lineages, havebeen much more elusive. In this issue, Zhanget al.7 and Calvi et al.8 now provide insightsinto the nature of HSC niches in adult animals. These authors demonstrate thatosteoblasts — cells that reside in the bonemarrow and secrete the calcified bone matrix— have a crucial role in HSC regulation.

Several studies have suggested that primi-tive HSCs reside next to the inner surface of bone and that they migrate towards theblood vessels at the centre of the bone marrow cavity as they mature and ‘differen-tiate’9,10. Since the 1970s, efforts to character-ize the HSC niche have involved developingsystems in vitro that might mimic some ofthe features of stem cell–niche interactionsin vivo11. Indeed, single clones of ‘stromal’cells can support HSC self-renewal and dif-ferentiation in culture12. And some of thesestromal cell clones are part of the bone-forming ‘osteoblastic’ lineage, which is con-sistent with the idea that osteoblasts might be a component of the HSC niche in vivo13.

Zhang et al.7 and Calvi et al.8 have nowconfirmed that osteoblasts have a function instem-cell regulation in animals. Both groupsemployed genetic strategies to increase the