This Week in Science

Science  05 Sep 2008:
Vol. 321, Issue 5894, pp. 1268
  1. Toward Precision Astronomy


    In a dynamical universe (one that is expanding), you would expect to see Doppler, or red shifts, of spectrograph lines of distant objects that are moving further and faster away from the observer, and for such shifts to drift in velocity over time. Determining the extent of velocity drift, however, requires a level of precision that has not been available—less than one centimeter per second per year. Steinmetz et al. (p. 1335; see the Perspective by Lopez) show how that situation may change using a laser frequency comb produced by an optic fiber. In a proof-of-principle experiment, they combine such a comb of equally spaced wavelengths with an astronomical observation (the Sun) to precisely measure and calibrate the wavelengths of the spectrogram.

  2. Moderating Rainfall

    Aerosols can either increase or decrease rainfall, so why do they act sometimes one way and sometimes another? Rosenfeld et al. (p. 1309) review the role of aerosols as moderators of precipitation, and propose a conceptual model to explain their apparently contradictory effects. Even small amounts of aerosols in very clean air prevent the development of long-lived clouds that can deliver large amounts of rain, whereas heavily polluted clouds evaporate much of their water before they can rain through a combination of microphysical and radiative effects. Thus, precipitation occurs most efficiently and abundantly at moderate aerosol concentrations.

  3. Back in Circulation

    The climate of the Mediterranean region during the Last Glacial Maximum, between 23,000 and 19,000 years ago, is known to be much colder than today, but the atmospheric circulation patterns that prevailed remain poorly understood. Kuhlemann et al. (p. 1338, published online 31 July) synthesized a range of new and published data on the equilibrium line altitude of glaciers (the altitude at which ice covers the ground all year long), paleoflora, and regional sea surface temperatures, and reconstructed the three-dimensional temperature structure of the atmosphere. Atmospheric circulation was like that observed commonly in the winters of the Little Ice Age, roughly between 1500 and 1900.

  4. Putting Limits on Ice Loss

    Ice loss from the margins of the Greenland and Antarctic ice sheets can occur through dynamically forced discharge from fast flowing ice streams and calving of marine-terminating glaciers. However, so little is known about ice sheet dynamics that models are unable to represent these processes accurately. Instead of trying to add up estimates of individual source contributions, Pfeffer et al. (p. 1340) calculated how much ice discharge from outlet glaciers in Greenland and Antarctica would be required to produce various rates of sea level rise, and then evaluate the plausibility of those discharge rates. Estimates of more than 2 meters of sea level rise by 2100 are highly unlikely—a more reasonable estimate is between 80 centimeters and 2 meters.

  5. Coding Space, Time, and Memory


    Mental operations such as planning, free recall, and problem-solving are assumed to depend on the central nervous system's self-organized sequences of activity, which permit cognitive representations, in sequence, of the future or the past. Similar cognitive content should be represented by similar assembly sequences, and different content should be distinguished by distinctive sequences. Experimental verification of this hypothesis has had to wait for large-scale assembly recordings. Pastalkova et al. (p. 1322; see the News story by Miller) report that, during the delay period of a memory task when an animal is running in a running wheel, each time point is characterized by the firing of a particular constellation of hippocampal neurons that form a highly specific activity sequence across time. During learning, the temporal order of multiple external events is instrumental in selecting the appropriate neuronal representations, whereas, during free recall or action planning, the intrinsic dynamics of the hippocampal system determines sequence identity.

  6. Focus on Fatty Acid Synthase

    Structural studies have led to an increased understanding of the large enzyme systems responsible for the synthesis of fatty acids, polyketides, and nonribosomal peptides. Now Maier et al. (p. 1315, see the cover and the Perspective by Smith and Sherman) report a structure of porcine fatty acid synthase (FAS) that includes five of seven catalytic domains, two nonenzymatic domains, and various linkers. The structure shows how the linker regions and catalytic domains are organized to provide the flexibility required for iterative fatty acid elongation. Like modular polyketide synthase, mammalian FAS acts as a “megasynthase” that can accommodate insertion or deletion of product modifying domains to allow generation of diverse products.

  7. Tracking Evolution of Transcription Regulation

    Bioinformatic approaches are providing insight into the evolution of noncoding regulatory elements of genes that can drive different expression outcomes from similar sets of genes (see the Perspective by Wray and Babbitt). Several recent computational efforts have identified conserved noncoding sequences that have evolved rapidly in humans, but it is not known whether their functions might have changed during the evolution process. Prabhakar et al. (p. 1346) used such a noncoding element called human-accelerated conserved noncoding sequence 1 (HACNS1), as well as orthologs of the gene from nonhuman primates, to create transgenic mouse embryos. HACSN1, but not the nonprimate orthologs, drove expression of a reporter gene at the junction of the anterior developing hand and forearm, including the base of the developing thumb and wrist. Sequence changes were identified that could “humanize” the expression patterns of the chimpanzee enhancer. Hong et al. (p. 1314) searched for clusters of potential transcription factor binding sites, in this case for targets of regulation by the transcription factor Dorsal and known cofactors in the fruit fly. Some of the secondary, or “shadow,” enhancers have patterns of gene expression that overlap those of primary enhancers, and may be able to evolve without disrupting core expression patterns.

  8. ESCRTing Membrane Scission


    So-called ESCRT proteins have been implicated in catalyzing different cellular and pathological processes, including multivesicular body biogenesis, retrovirus budding, and cytokinesis. These processes involve topologically similar membrane events that require a common final abscission step to separate two newly formed membrane-enveloped structures. Little is known regarding how the budding steps, including membrane abscission, are catalyzed. Indirect evidence suggests that ESCRT-III plays an important role in the final step. Notably, dominant-negative CHMP3, a subunit of ESCRT-III, inhibits HIV-1 budding as well as cytokinesis. Because cytokinesis does not require vesicle formation, it would seem that ESCRT-III regulates steps in membrane abscission. Lata et al. (p. 1354, published online 7 August) provide structural evidence for the formation of distinct heteromeric ESCRT-III assemblies by electron microscopy. These structures could bind on the inside of the neck of a bud or at the midbody between dividing cells and regulate membrane abscission.

  9. The Normal Side of Trans-Splicing

    Human tumors frequently display chromosomal rearrangements that fuse two distinct genes and result in the expression of chimeric messenger RNA (mRNA) transcripts whose protein products are oncogenic. Li et al. (p. 1357; see Perspective by Rowley and Blumenthal) suggest that the chimeric mRNAs generated by chromosomal rearrangements in tumors may sometimes represent constitutively expressed versions of chimeric mRNAs generated in healthy tissue by trans-splicing. Studying a JAZF1-JJAZ1 chimeric transcript that is abundantly expressed in human endometrial stromal sarcomas with a (7;17) chromosomal translocation, the authors found unexpectedly that the same chimeric transcript was expressed in normal endometrial stromal cells, even though these cells lacked the chromosomal translocation. In normal cells, the chimeric transcript arose by trans-splicing between independently transcribed JAZF1 and JJAZ1 pre-mRNAs, and it was translated into a chimeric protein of unknown function. Trans-splicing is thought to be a rare event in mammalian cells, but these results suggest that other examples might be found by searching for normal RNA counterparts to the many chimeric mRNAs generated by chromosomal rearrangements in tumors.

  10. Quantity, Not Just Quality, Matters

    Colorectal cancer is one of the leading causes of cancer-related deaths worldwide. Because 20 to 30% of cases occur in individuals with a family history of the disease, genetic factors are thought to be a substantial contributor to risk. Valle et al. (p. 1361, published online 14 August) now report that one of these factors is an inherited variation in the expression level of a gene encoding a key signaling protein previously implicated in colorectal cancer pathogenesis. Within a Caucasian population in the United States, individuals with colorectal cancer are 5 to 10 times more likely than controls to show germline allele-specific expression of the TGFBR1 gene, which encodes the type I receptor for transforming growth factor-β. Allele-specific expression appears to result in a modest, but biologically meaningful, lifelong reduction in the expression of TGFBR1, which in turn confers an increased risk of colorectal cancer. Thus, it seems that the genetic contribution to disease risk includes not only mutations that abolish or modify the function of genes but also more subtle alterations that change the baseline expression levels of genes.

  11. Explaining Meteorite Oxygen Isotope Composition

    Early meteorites show a wide variation in their relative abundances of the three isotopes of oxygen. These variations have generally been explained as a result of self-shielding, in which absorption of light by abundant 16O atoms from CO, the most abundant oxygen source in the early planetary nebula, saturates. Equal dissociation of the heavier Co molecules containing 17O and 18O atoms leads their mass-independent fractionation. Chakraborty et al. (p. 1328) provide a test of this process in a synchrotron radiation in an experiment that mimics the dissociation of CO in the early solar system. They see a large fractionation in their experiments that occurs at wavelengths inconsistent with expectations from self-shielding. Instead, the data imply that fractionation reflects spin-orbital coupling in an excited predissociation state.

  12. The Active Part of Real Catalysts

    Many industrial catalysts consist of metal nanoparticles on oxide supports, and in many cases this morphology increases the activity of the metal by increasing its surface area relative to the bulk metal, so that smaller particles are more active only in that more metal atoms are exposed. However, if there are electronic interactions between the oxide support (at defects or oxygen vacancies), then it is possible that a small fraction of metal particles account for most of the activity of the catalyst. Herzing et al. (p. 1331) found large differences in activity for two gold nanoparticles—iron oxide catalysts for the low temperature oxidation of CO that varied only their final preparation step (a drying procedure). High-resolution microscopy that allowed the enumeration of the various gold species, from atoms to nanoparticles, indicated that the activity varied mainly with the presence of bilayer gold nanoparticles, as has been found in studies of simpler model catalysts.

  13. Viral Resistance Strategy

    Understanding the nature of host viral resistance factors has provided important insights into antiviral immunity. Certain host genes are known that protect mice against Friend retrovirus infection, but the identity of one of these factors, “Recovery from Friend virus (FV) gene 3,” (Rfv3)—which alleviates viremia and promotes the appearance of FV-specific neutralizing antibodies—has been elusive. Santiago et al. (p. 1343) now show that the autosomal gene encoding Rfv3 is murine Apobec3, member of a family of deoxycytidine deaminases known for their antiviral activity, as well as for their roles in somatic hypermutation and antibody class-switching. Perhaps human Apobec3 may have a similar role in promoting an effective humoral immune response against HIV-1.

  14. Wnt Receptor Signaling

    Wnt glycoproteins act as important signaling molecules in a range of processes from development to cancer. Pan et al. (p. 1350) describe a missing link in the mechanism by which Wnt binding to its receptors initiates biochemical signaling within cells. They identified phosphatidylinositol-4-phosphate 5-kinase type I (PIP5KI) in a screen for components required for Wnt signaling in human cells. After activation, the Wnt receptor LRP6 becomes phosphorylated on serine and threonine residues, and PIP5KI was required for this event. The Wnt signaling component dishevelled, a scaffold protein, interacted with PIP5KI, and dishevelled and the Wnt receptor protein frizzled were required for Wnt-dependent formation of phosphatidylinositol 4,5-bisphosphates [PtdIns (4,5)P2]. Accumulation of PtdIns (4,5)P2 appeared to be necessary for the aggregation of LRP6 and its consequent phosphorylation.