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Stretched out completely, a human chromosome would be several centimeters long. It is packed, along with its 45 companions, into a few-microns-wide cell nucleus in such a way that all the necessary genes are accessible to RNA transcription. Figuring out how that packing is done is no easy task. Microscopy helps, but provides nowhere near a complete picture. Now a research team led by Eric Lander of MIT and Job Dekker of the University of Massachusetts has developed a method for probing chromosomes’ folded structures. The researchers chemically join segments of a folded chromosome that are close in space, cut away and sequence the DNA around the crosslink, and compare those sequences to genome libraries to determine which parts of the chromosome are in contact. A matrix of the observed contacts, as shown in the figure, reveals large-scale organization. Analyzing the plaid pattern, the researchers found that most of the cell’s actively transcribed DNA was spatially segregated from most of the inactive DNA. On a smaller scale, chromosome segments a millimeter or so in extended length appeared to form so-called fractal globules with self-similar structures very different from that of a tangled polymer in equilibrium. So far, the researchers have studied only cultured cell lines: one derived from a tumor and another modified by a virus. They hope to apply their method to healthy cells and to look for differences in chromosome structure among cells of different types. (E. Lieberman-Aiden et al., Science 326, 289, 2009.) —Johanna Miller

Photonic devices that can detect and control the polarization of light across a range of wavelengths are rare. More common are materials such as quartz that can be made into monochromatic optical retarders, which through their intrinsic birefringence convert a specific wavelength of linearly polarized light into circularly polarized light, or vice versa. Some multilayered thin films exhibit achromatic retardation through fabricated periodic nanoscale structures that effectively combine the dispersive properties of each layer to achieve wavelength-independent birefringence. But engineering nanoscale structures is tricky, and even the best synthetic achromatic retarders perform poorly across the full visible range, varying by as much as 9.1°. But Nature has already solved the puzzle in animals that have evolved biophotonic structures for signaling, vision, and coloration (see Physics Today, January 2004, page 18). Now, an international team of researchers from the UK, Australia, and the US has discovered a near-ideal achromatic retarder in the eyes of the colorful peacock mantis shrimp, Odontodactylus scyllarus, shown in the image. This mantis shrimp’s biophotonic retarder is the R8 photoreceptor cell—a UV-photopigment-filled lipid bundle with critical radii of 26 nm and 40 nm, which are subwavelength for visible light. When subjected to linearly polarized light, the R8 cell acted as a quarter-wave retarder, converting the incident light to circularly polarized light, as confirmed by close experimental agreement with theoretically determined Stokes parameter values. Moreover, the extent of retardation varied by only 2.7° across the visible spectrum. (N. W. Roberts et al., Nat. Photonics, in press, doi:10.1038/nphoton.2009.189. Image courtesy of Roy Caldwell, University of California Berkeley.)—Jermey N. A. Matthews

In a single cell, thousands of simultaneously occurring biochemical reactions carry out such functions as converting and storing energy and regulating nutrient levels; together, those processes make up the cell’s metabolic network. Computational biology involves, among other things, the linking of metabolic pathways to form a metabolic network model, a promising tool for preclinical drug studies and other medical research. However, such computational models do not traditionally include the function-determining structural details of a network’s macromolecules; for example, an enzyme’s ability to catalyze reactions and regulate the cell’s response to external stimuli is determined by its three-dimensional configuration. Now, an international team led by Adam Godzik at the Burnham Institute for Medical Research in California has taken a rare step and introduced atomic-level protein structural data to the metabolic network model of an ancient thermophilic bacterium, Thermotoga maritima, shown in this optical microscope image. The image also shows schematics of proteins in their 3D configurations, which, when they were expressed in the reconstructed metabolic network, helped the research team solve the puzzle of how proteins evolve when their cell networks grow larger.

It turns out that only 37% of T. maritima’s proteins are essential to the formation of its metabolic network; those “core-essential” proteins adopt the bulk—61%—of the bacterium’s relatively few unique 3D configurations. The finding suggests that the core-essential proteins evolved their structure to perform additional functions in distinct pathways. (Y. Zhang et al., Science 325, 1544, 2009.)—Jermey N.A. Matthews

When a person’s head strikes, or is struck by, another object, it accelerates. As it begins to decelerate, the brain slams into the skull, then bounces off and oscillates until the impact energy dissipates. The resulting shear and compressive strains can lead to brain damage. But in battlefield explosions, just the acoustic waves alone can cause soldiers traumatic brain injuries. To better understand that process, Lawrence Livermore National Laboratory's William Moss and Michael King and the University of Rochester’s Eric Blackman compared numerical simulations of a head colliding with a wall to one being struck by an explosion’s blast waves. Despite accelerating the head at less than half the rate of the wall collision, the simulated blast produced on the brain surprisingly comparable pressure spikes—ranging up to 3 bars—and even larger pressure gradients. Apparently, those mechanical loads are delivered by the skull, which ripples under the pressure of blast waves—the rippling motion is indicated in the image by velocity vectors. The researchers confirmed the role of the skull’s elasticity by making it 1000 times stiffer in their simulations and observing a fivefold drop in the pressure spikes. The simulations also revealed that helmets in contact with the head can impart an additional mechanical load to the skull and helmets that allow for an air cushion geometrically focus and increase the magnitude of blast waves. (W. C. Moss et al., Phys. Rev. Lett., in press.)—Jermey N. A. Matthews

Dispersed in the brains of Alzheimer's patients are disk-shaped lesions, about 100 µm across. Whether those lesions, or plaques, are a cause or a consequence of Alzheimer's disease is controversial, but their composition is clear. The plaques are made from fibrous aggregates—amyloid—of protein or their shorter cousins, peptides. Once sequestered in amyloid, a protein or a peptide can no longer perform its function. Even if amyloid does not directly cause Alzheimer's and other diseases, it seems at best a useless, dead-end repository of proteinaceous material. But as a new paper exemplifies, a less malign view of amyloid is emerging. Roland Riek of ETH Zürich and his collaborators have demonstrated that our bodies exploit amyloid as a temporary storage medium for a wide range of peptide hormones. Riek suspected a hormone–amyloid connection when he found that a stress hormone formed amyloid fibrils. He and his collaborators then subjected 41 other peptide hormones to a battery of biochemical, biophysical, and crystallographic tests. The finding: 75% of the peptide hormones form amyloid; and, as befits a storage medium, the amyloid can also disaggregate to release the peptides. In a final test, the team stained slices of mouse brain with hormone-sensitive and amyloid-sensitive dyes. The stained regions coincided. Riek's discovery adds to the modest but growing list of examples of so-called functional amyloid that perform useful tasks in living organisms. Evidently, amyloid is not always pernicious. (S. K. Maji et al., Science 325, 328, 2009.)—Charles Day

The late 19th century saw a radical innovation in horse racing: Jockeys abandoned a comfortable, upright posture for the hunched-over, short-stirrup style seen today at racetracks (and in the figure). By 1910, when the style was universally adopted, race times had dropped by more than 5%; the improvement in the first decade of the 20th century was greater than in the hundred years since. One might think that the reduced aerodynamic drag of the new style led to the faster times, but Thilo Pfau and colleagues at the University of London’s Royal Veterinary College suggest that the way the modern jockey moves in response to the horse’s galloping makes the more significant contribution. The London group measured the motion of jockeys and horses and observed that jockeys do not suffer much vertical displacement as a horse races—a consequence of the way they absorb the horse’s motion by strenuously pumping their legs while riding. So, though the horse supports the jockey’s weight, it does not expend unnecessary energy lifting and lowering its cargo. Moreover, the horse’s forward speed varies over the course of a gallop cycle. When the horse is moving faster than on average, the jockey moves slower. That out-of-phase response could help the horse to execute a smoother, more energy-efficient gallop. (T. Pfau et al., Science 325, 289, 2009; photo by Pharaoh Hound) —Steven K. Blau

Lactose isn't present in our guts all the time. To ingest it and other occasional sources of nutrition, Escherichia coli (see figure) must detect the molecules and then make the proteins that help harvest them. That process of on-demand protein production is called gene regulation. It's the subject of a new quantitative analysis by physicists Ulrich Gerland of the University of Munich, Germany and Terence Hwa of the University of California, San Diego. E. coli uses two modes of gene regulation. In (+ +) control, proteins called transcription factors float freely in the cell. When a TF molecule meets its molecular target—lactose, say—it locks onto the appropriate region of the bacterium's DNA and triggers the production of the appropriate protein. In (− −) control, the TF is usually bound to the DNA and blocks protein production until TF's molecular target arrives to detach the TF and lift the block. Both modes are equally effective. When does evolution favor one over the other? The answer, according to Gerland and Hwa, depends on a tug of war between two competing selection principles. The use-it-or-lose-it principle favors (+ +) control during feasts and (− −) control during famines, whereas the wear-and-tear principle favors the opposite. Both selection principles mitigate the adverse effects of genetic mutation but, as Gerland and Hwa found, whether one prevails over the other depends on the size and age of the colony and on how rapidly the food supply fluctuates. Besides quantifying gene regulation, Gerland and Hwa's analysis might help pharmacologists understand and combat the resistance of bacteria to antibiotics. One strain of E. coli, called mar, is resistant to tetracycline, an otherwise potent antibiotic, due to the working of two transcription factors. (U. Gerland, T. Hwa, Proc. Natl. Acad. Sci. USA 106, 8841, 2009.) —Charles Day

Traveling smoothly through a turbulent medium is no mean feat, as anyone who regularly flies in an airplane can attest. Scientists have investigated how fish navigate through turbulent currents, but until recently they had not addressed the analogous issue of animal flight through turbulent air. Now biologist Stacey Combes has filmed male orchid bees (genus Euglossa) flying in turbulent airstreams and, with colleague Robert Dudley, has described the effects of the turbulent air on the bee’s flight stability and maximum speed. Combes induced the bees to fly in a turbulent airstream by luring them with an attractive scent. As the airspeed increased, the bees found it increasingly difficult to avoid the rolling illustrated in the left image. When the airspeed was high enough and maintaining stable flight difficult enough, the bees extended their hind legs, as depicted in the right photograph.

That move increased the moment of inertia about the roll axis by roughly 50% and improved stability, but it also increased body drag and energy expenditure by about 30%. In a second experiment, Combes altered the turbulence of the stream by inserting different geometric grids. Bees flying in the lower-turbulence environment were able to reach higher speeds before instabilities caused them to be ejected from the air stream. (S. A. Combes, R. Dudley, Proc. Natl. Acad. Sci. USA, doi:10.1073/pnas.0902186106.) —Steven K. Blau

Related link: Dragonfly Flight, Z. Jane Wang, Physics Today October 2008, page 74.

The unusual stiffness or sponginess of dead and decaying biological tissue is readily apparent to the human touch. However, early detection of such mechanical property changes in a tissue's extracellular matrix could signal the onset of disease. To measure the elasticity of tissue in living patients, needle-based indentation methods are more direct and less expensive alternatives to MRI, ultrasound, and electrical impedance. Such a probe has recently been developed by University of California, Santa Barbara, physicist Paul Hansma, an atomic force microscopy expert, and his collaborators. The handheld tissue diagnostic instrument (TDI) consists of a stainless steel probe, 175 µm to 1 mm in diameter depending on the tissue sample, which longitudinally oscillates at 4 Hz in a needle-thin stationary sheath. The force from the magnetically controlled oscillation of the probe produces a corresponding displacement in the tissue. The tissue's elastic modulus, or stiffness, is proportional to the slope of the force-displacement curve, and energy dissipation in the tissue is proportional to the area under that curve. The researchers measured, with millimeter spatial resolution, healthy and diseased tissue samples ranging in elastic moduli from around 1 kPa to 12 GPa. Among them were mouse breast tissue, which hardens when it becomes tumorous, and human tooth dentin (see schematic), which softens and decays when infection sets in. The researchers say the instrument could be used in the future to simultaneously test and biopsy a tumor or, if the probe is coated with antibodies, to measure single-molecule interaction forces. (P. Hansma et al., Rev. Sci. Instrum., in press.) — Jermey N. A. Matthews

The venoms from spiders, scorpions, some marine snails, and certain other animals immobilize victims by blocking ion channels that control nerve cells. The bioactive molecules in the venoms are incredibly diverse—cone snails alone produce more than 50 000 distinct peptide venoms—and researchers hope to mine them for potential pharmaceuticals that, say, kill pain or unlock diseased ion channels. Knowing the amino acid sequences would help in that effort. Typically, researchers turn to mass spectrometry, in which the peptides are fragmented and the amino acid sequence deduced, usually in combination with searching a protein database. Unfortunately, the organisms do not have sequenced genomes, so the amino acid sequence has to be determined from mass spectrometry alone. Such de novo sequencing has been hampered by an inability to produce sufficient fragmentation. Now, Beatrix Ueberheide, David Fenyö, and Brian Chait of the Rockefeller University and Paul Alewood of the University of Queensland have devised a method that solves that problem. They realized that a simple chemical trick—the conversion of cysteine, an abundant amino acid in peptide venoms, to a lysine-like charged residue—would put the molecules in a highly positively charged state. They could then be more efficiently fragmented using a technique known as electron transfer dissociation and give rise to a rich mass spectrum. As proof of principle, the team reconstructed the complete sequence for 31 distinct peptide toxins using just 7% of the venom from the gland of a single cone snail. (B. M. Ueberheide et al., Proc. Natl. Acad. Sci. USA , in press.) — R. Mark Wilson