This Week in Science

Science  20 Feb 2004:
Vol. 303, Issue 5661, pp. 1101
  1. Sex and Repression

    Males and females of mammals, flies, and worms differ in their X chromosome content. In each species, an essential X chromosome-wide process of dosage compensation ensures that cells of either sex express equal levels of X-linked gene products. In the nematode worm, Caenorhabditis elegans, a dosage compensation protein complex is recruited to X chromosomes of hermaphrodites to repress transcription by half, but the mechanism for this recruitment has been unclear. Csankovszki et al. (p. 1182; see the Perspective by Alekseyenko and Kuroda) assayed specific regions of the X chromosome for their ability to bind the dosage compensation complex. Multiple X regions recruited the complex to specific recognition elements distributed throughout the X chromosome. From these nucleation sites, the complex spread to regions that lacked X-recognition sites. Thus, discrete cis-acting sites on the X chromosome distinguish it from autosomes for the recruitment of the dosage compensation complex.

  2. Double Pulsar

    Observations with the Parkes and Jodrell Bank radio telescopes by Lyne et al. (p. 1153; see the cover, the Perspective by van den Heuvel, and the 9 January news story by Irion) have revealed a rare system of two pulsars. A 2.8-second pulsar, J0737-3039B, and a 23-millisecond pulsar, J0737-3039A, are in a close binary system, and B eclipses A on every orbit, which allows the magnetospheric structure to be studied in detail. Pulsar B has a lower mass as well as different magnetic field and spin-down properties. These results can be used to refine models of the formation of rare systems in which two supernovae explode at different times and become more tightly bound after the progenitors collapse to form spinning neutron stars. Such binary systems can also be used to study general relativity and to detect gravitational wave emissions.

  3. Particle Chemistry

    Aerosol particles influence climate by acting as cloud condensation nuclei and by scattering and absorbing solar radiation. Secondary organic aerosols (SOAs) form through chemical reactions from volatile organic compounds (VOCs). The biogenic VOC isoprene makes up nearly 50% of the non-methane atmospheric hydrocarbons, but has been assumed not to create SOAs because its reaction products have vapor pressures too high to allow them to be adsorbed onto particles. Claeys et al. (p. 1173) observed polyol compounds that appear to have been produced by the photooxidation of isoprene that have vapor pressures low enough for them to be condensed onto preexisting aerosols. Measurements of the abundance of these compounds suggest that these products could contribute between 5 and 20% of the annual SOA production from biogenic sources.

  4. Clumpy Stellar Precursors

    More massive stars (greater than 8 solar masses) tend to form in giant clusters of gas and dust, and its not clear if the disk-accretion star formation mechanism works in such an environment. Beuther and Schilke (p. 1167) used high-spatial-resolution interferometry to examine the structure of the massive cluster, IRAS 19410+2336. They distinguished dusty cores with gaseous halos that, based on their morphology and mass distribution, would tend to form stars by disk-accretion processes. Thus, stars can form by the same mechanism regardless of their environment.

  5. I Feel Your Pain

    Context often provides an important clue to figure out what a person means when they report feeling pain—a painful sensation, such as an electric shock, versus an emotionally unsettling feeling, such as heartache. Sometimes, an apparently painful stimulus can be alleviated by top-down control, e.g., when an inert pill or placebo produces an analgesic response. Two groups have explored the cortical pathways mediating the two components of pain, the affective and cognitive (see the news story by Holden). Singer et al. (p. 1157) found that the anterior insula and anterior cingulate regions were active when women observed their partners receiving an electric shock; the extent of activity in these regions correlated with an individual woman's empathy score. Wager et al. (p. 1162) found that administration of a placebo activated the dorsolateral prefrontal cortex and that the activity in this region was inversely related to the activity within the pain matrix—a set of brain regions known to subserve the sensory component of pain—and thus correlated with the extent of analgesia reported.

  6. Mapping Out Molecular Turns

    The conformational flexibility of small biomolecules underlies polymer and protein folding, but the energetic barriers to rotation about a single bond can be extremely low. Thus, any direct method for exciting only one bond rotation must use small amounts of energy. Dian et al. (p. 1169) have improved on a method in which carbon-hydrogen stretching modes were used to excite conformational changes in cold gas-phase molecules. By using stimulated emission pumping, they can access energies from the zero-point level through 1500 wave numbers, to study tryptamine. They observe seven conformational minima and map out several barriers on the isomerization pathways between the different conformers that normally would be thermally populated.

  7. Precise Locations of Repeating Events

    Locating seismic events with greater precision is necessary to determine the source of the energy. Schaff and Richards (p. 1176) use cross-correlation of seismograms on a relatively large scale to locate 14,000 events in and near China. About 10% of these precisely located epicenters had similar waveforms, and thus their sources are within about 100 meters of each other. These doublets or multiplets are either man-made explosions that can be monitored with this technique, or earthquakes on a specific fault that provide information about tectonic structures.

  8. De Novo Disulfide Pathway

    Disulfide bonds are important to the structural integrity of many secreted proteins. In Escherichia coli, disulfide bond formation is mediated by the periplasmic protein DsbA, which in turn is recycled by the membrane enzyme DsbB. Now, Masip et al. (p. 1185) have engineered a new pathway for disulfide bond formation. By imposing evolutionary pressure, they generated a mutant of thioredoxin that forms a [2Fe-2S] bridged dimer. In vitro, the iron-sulfur form of thioredoxin can catalyze oxidative folding of the substrate protein hirudin. When transported through the Tat pathway, the [2Fe-2S] thioredoxin can generate disulfide bonds in the periplasm of E. coli that lacked the DsbA-DsbB catalytic system.

  9. Gaining Access

    Unlike other nonprimate lentiviruses, feline immunodeficiency virus (FIV) induces a disease similar to AIDS in its natural host, the domestic cat. However, relatively little is known about how FIV infects helper T cells of the immune system. Shimojima et al. (p. 1192) observed that feline CD134 specifically facilitated infection of cells by FIV, requiring coexpression of the equivalent chemokine receptor used by X4 strains of HIV. The close evolutionary relationship between HIV and FIV and their functionally related, yet distinct, modes of cell entry have broad implications for understanding the evolution and biology of HIV infection and pathogenesis.

  10. Resistin' a Knockout

    Obesity is one of the most potent risk factors for insulin resistance and type 2 diabetes, but the molecular mechanisms underlying this link are poorly understood. The fat-derived hormone resistin has been postulated to be part of that mechanism but its role in glucose homeostasis has been controversial. Banerjee et al. (p. 1195) now show that mice lacking resistin have low fasted blood glucose levels caused by reduced glucose production in the liver. Resistin null mice fed a high-fat diet were less prone to exhibit the elevated glucose levels seen in wild-type mice on a similar diet, which supports the idea that resistin mediates the hyperglycemia associated with obesity. These results will likely stimulate further research exploring whether resistin has a comparable role in humans.

  11. Controlling Cholesterol Uptake

    The statins, a class of widely prescribed drugs that inhibit cholesterol biosynthesis, have proved very effective in reducing serum levels of cholesterol. However, because statins are not safe for all patients, and because not all patients respond to these drugs, alternative cholesterol-lowering strategies are being sought. In a study exploring the mechanism by which dietary cholesterol is absorbed from the intestine, Altmann et al. (p. 1201; see the Perspective by Klett and Patel) identified a protein, NPC1L1 (Niemann-Pick C1 Like 1), with sequence and expression features expected of an intestinal cholesterol transporter. Mice genetically deficient in NPC1L1 exhibited a 70% reduction in absorbed cholesterol and were insensitive to ezetimibe, a drug that blocks cholesterol absorption but whose molecular target is unknown. Further analysis of NPC1L1 and other proteins in its cellular pathway may lead to more effective drugs for cholesterol management.

  12. Observing the Intention to Move

    What would we expect to find if it were possible to trace an arm movement back to its origins? Prior to the actual movement, we would find the preparative stages of visualizing the target and planning the trajectory for our arm. Lau et al. (p. 1208; see the Perspective by Eagleman) have looked further back in time, using a well-established behavioral task, and identified a neural trace of an intention to make a movement, reflected as a heightened activation of the pre-supplementary motor area (pre-SMA). Stronger connectivity occurred between the prefrontal cortex and the pre-SMA when subjects were asked to pay attention to becoming aware of their intention to move, as opposed to making the movement itself.

  13. Tumor Suppressor Doing Double Duty

    The tumor suppressor protein PTEN is a dual-specificity phosphatase whose catalytic domain acts primarily on lipids but can also target proteins. Raftopoulou et al. (p. 1179) report that PTEN lipid phosphatase activity is not required for PTEN to inhibit cell migration. Instead, its protein phosphatase activity is required to dephosphorylate a single residue in its C-terminal tail, which in turn regulates migration. This mechanism may contribute to the progression of tumors that harbor catalytically inactive forms of PTEN.

  14. Breaching the Defense

    Mycobacteria are of particular interest because there is a resurgence of tuberculosis worldwide. These bacteria live behind an outer membrane fortification, composed largely of hydrophobic mycolic acid chains; the low permeability of this barrier accounts for their slow growth rate and their relative insensitivity to antibiotics. Faller et al. (p. 1189) present the crystal structure of one of the few pathways across this mycolic moat, the porin MspA. Like other porins, a barrel of β-strands is the primary motif; however, unlike known porin structures, MspA is organized into two stacked barrels with a distal globular domain. All together, the MspA octamer looks like a goblet, with the mouth pointing outward and the narrowest portion, the base, facing inward.

  15. Fixing Osteogenesis Imperfecta

    Osteogenesis imperfecta is caused by mutations in genes encoding type I collagen and is characterized by abnormally fragile bones. Chamberlain et al. (p. 1198) isolated mesenchymal stem cells from adults with the disease and showed that the mutant genes could be targeted with adeno-associated viral vectors. Collagen synthesized by these cells after gene targeting had improved assembly and stability, and produced fibrils closer to normal size in culture. The targeted cells could still form bone in implanted, immunodeficient mice. In the future, gene targeting of adult stem cells may overcome limitations of using embryonic cells and decrease the risks associated with random gene integration in patients.

  16. The Missing Link

    Two signaling pathways that control axon guidance are the cyclic nucleotide-protein kinase A (PKA) pathway and a pathway controlled by Plexin A, a guidance receptor that responds to the repulsive guidance cue Semaphorin 1-a. Terman and Kolodkin (p. 1204) have determined that a single protein, Nervy, links these two pathways in Drosophila neurons. Nervy is an A Kinase anchoring protein that binds to both PKA and to Plexin A. When not bound to PKA, Nervy antagonizes both axonal repulsion and Plexin A signaling.