This Week in Science

Science  12 Nov 1999:
Vol. 286, Issue 5443, pp. 1253
  1. A Solid-Solid Transition at D"

    Just above the outer liquid iron core lies a thin layer in the solid silicate mantle, called D”, that is seismically anomalous. The nature of this important coupling layer between the core and the mantle remains poorly defined. Sidorin et al. (p. 1326) combined global tomographic models with waveform analysis of seismic phases that sample the D” layer to derive a consistent model for its structure. A solid-to-solid phase transition at about 200 kilometers above the core mantle boundary provides the most plausible explanation for the data they analyzed. They suggest that D” is a region that varies in elevation above the core and that represents the third major discontinuity. Additional experimental data will be needed to characterize the minerals involved in this proposed transition.

  2. Rapid Melting Revealed

    Melting of a solid normally involves nucleation of the liquid phase at defects or inclusions at its surface. However, if heated rapidly enough with sufficiently high energy, a semiconductor surface can melt completely and homogenously before thermal processes can begin to relax the process. Observing the loss of crystalline order directly requires extremely fast x-ray diffraction methods. Siders et al. (p. 1340; see the Perspective by Nelson) have now used picosecond x-ray pulses to observe such nonthermal melting in single-crystal films of germanium.

  3. HIV Moves In

    Two surprising pieces of information concerning the early events in human immunodeficiency virus-type 1 infection have been obtained by Zhang et al. (p. 1353) from an animal model of heterosexual viral transmission. They found that lymphocytes, rather than macrophages or dendritic cells, were the first cells infected when the virus was inoculated intravaginally. Furthermore, many of the infected cells were quiescent rather than actively dividing, as evidenced by the absence of early molecular markers of proliferation. Infected resting cells could still be found in lymph node biopsies of human patients after treatment with antiretroviral therapy. Understanding the state of this infected cell population is important to efforts directed at eradication of the virus from cellular reservoirs.

  4. Sauropod Variation

    Several newly identified Cretaceous-aged sauropod dinosaurs from the Sahara are reported by Sereno et al. (p. 1342). As a group, these sauropods, which range in age from 130 to 100 million years ago, seem to be relatively primitive compared to those on other continents. These data and comparison with other sauropods imply that the rate of skeletal evolution among these large dinosaurs was quite uneven.

  5. Effective Even on the Fringe

    Magnetic tunnel junctions can provide “nonvolatile” dynamic memory elements that remain in their on or off state even when power is lost. In spin-dependent magnetic tunnel junctions, which consist of a magnetically hard reference layer and a switchable magnetically soft layer, magnetization in the hard reference layer decays with increasing switching cycles, despite the magnetic fields being considerably smaller than those required to switch the entire hard layer. McCartney et al. (p. 1337), using a magnetic imaging technique, identified large fringing magnetic fields that developed at the domain walls of the magnetically soft layer as the source of the decay of the magnetization. This finding should allow for the design of better magnetic memories.

  6. Making the Tag

    The targeted degradation of proteins has emerged as an important regulatory mechanism in a variety of cellular processes. Proteolysis is initiated by covalent tagging of the protein with ubiquitin, which is the signal recognized by the degradation machinery. The enzymes that catalyze the addition of ubiquitin are known as ubiquitin-protein ligases; one of these, E6AP, mediates the degradation of the tumor suppressor p53 in most cervical carcinomas. Huang et al. (p. 1321) describe the crystal structure of the catalytic domain of E6AP alone and in complex with the ubiquitin-conjugating enzyme that serves to provide activated ubiquitin to the ligase.

  7. Mitochondria in Action

    Intracellular calcium stores play a crucial role in the function of excitable cells. An important part of this calcium storage system are the mitochondria, which provide the cell with energy. Jonas et al. (p. 1347) have demonstrated in vivo a physiological link between excitation of the cell membrane and mitochondrial electrical activity. They succeeded in recording signals from mitochondria in intact presynaptic boutons of the squid giant synapse. After neuronal stimulation, they saw a calcium-dependent increase in mitochondrial ion channel activity.

  8. Pinpointing Rsks

    During development, some neurons undergo cell death if they are deprived of growth factors. Signals that contribute to such growth factor-dependent survival are mediated, at least in part, by activation of mitogen-activated protein kinases (MAPKs), but the crucial target of the MAPKs has been unknown. Bonni et al. (p. 1358) report that the protein kinase Rsk2 (a member of the pp90 ribosomal protein S6 kinase family), which is phosphorylated and activated by MAPKs, may mediate the effects on cell survival in cerebellar granule neurons exposed to brain-derived neurotrophic factor. Rsk 2 appears to have two ways of influencing cell survival: It phosphorylates and thus suppresses the effects of BAD, a protein that promotes apoptosis. Rsk2 also phosphorylates and activates the transcription factor CREB (cAMP response element binding protein). Activation of CREB may in turn enhance expression of Bcl2, a protein that promotes cell survival. In a Perspective, Nebreda and Gavin discuss these findings and those from a pair of reports that define another role of Rsks in the control of the cell cycle. Before fertilization, most vertebrate eggs are at metaphase of meiosis II. Cytostatic factor (CSF) is the name given to an enzymatic activity present in such eggs, which, when injected into dividing embryos, causes mitotic arrest in metaphase. Such “CSF arrest” can be initiated by the protein kinase Mos, which activates the sequential activation of MAPK kinase MEK and the p42 MAPK. The critical target of p42 MAPK has now been identified as the protein kinase p90 Rsk. Bhatt and Ferrell (p. 1362) show that depletion of Rsk from Xenopus egg extracts prevents mitotic arrest in response to activated Mos. Gross et al. (p. 1365; see the cover) demonstrate that activation of Rsk requires its phosphorylation by p42 MAPK and the 3-phosphatidylinositol-dependent kinase-1 (PDK-1). They also constructed a constitutively active form of Rsk that caused metaphase arrest when infected into blastomeres of two-cell Xenopus embryos. Activation of Rsk is thus necessary and sufficient to cause CSF arrest.

  9. Wake Me When You Need Me

    Regulatory proteins have generally been thought of as constitutively active. Puigserver et al. (p. 1368) now show that coactivators are actually inactive if they are not associated with their complementary DNA-binding proteins. Once a transcription factor and its coactivator unite, a conformational change in the coactivator occurs that leads to recruitment of additional coactivators such as the histone acetyltransferases SRC-1 and p300/CBP. Hence, transcription factor docking provides a specificity mechanism.

  10. Remember Those Shots?

    Vaccination enables an immune response to be mounted quickly upon exposure to the pathogen. This accelerated response is a result of a “memory” being established in the appropriate lymphocytes. It has been thought that T cell memory persistence requires the T cell's antigen receptor to either see antigen or at least major histocompatibility complex (MHC) proteins. Swain et al. (p. 1381) studied the memory requirements of CD4 T cells, and Murali-Krishna et al. (p. 1377) studied those of CD8 T cells. Neither subset requires MHC proteins or antigen to be maintained. An understanding of what generates such memory and how it is maintained will lay the groundwork for the development of more efficacious vaccination strategies (see the news story by Hagmann).

  11. A Single Parent

    Carbonaceous chondrites are primitive meteorites, possibly the first major components that formed in the solar nebula, accreted into planetesimals (or parent bodies). The carbonaceous chondrites are divided into subgroups based on their mineralogy and oxygen isotopic compositions, and these different subgroups were thought to be derived from different parent bodies in the solar nebula. Recent work has suggested that the oxygen isotopic differences may be related to secondary aqueous alteration on the parent body. Young et al. (p. 1331) developed a finite-difference fluid flow model for a fictive parent body and showed that the radial flow of liquid water along a thermal gradient in the parent body can explain the oxygen isotopic signatures of the three most distinctive types of carbonaceous chondrites (the CV, CM, and CI groups). Thus, the oxygen isotopic character of the carbonaceous chondrites may have evolved from a single parent body. This possibility may help refine simulations of the formation of the solar system.

  12. Dirty Details

    Much of the organic matter in soil is lumped together as “humic substances,” the natural organic polyelectrolytes formed from the decay of plant and animal remains. These difficult-to-characterize substances can hold the key to understanding issues ranging from carbon cycling in soils to soil productivity. Myneni et al. (p. 1335) show how in situ spectrometry can reveal the distribution of structures of humic substances in soils. Their data show that the simple picture that humic substances are coils in acidic soils and elongated structures in alkaline soils is incomplete.

  13. Mapping the Malaria Parasite

    A genetic linkage map has been constructed by Su et al. (p. 1351) for the genome of Plasmodium falciparum, which causes malaria. Markers had an average spacing of 30 kilobases within the 25- to 30-megabase genome. The map pinpoints potential hotspots of recombination and will be useful for sequencing projects and for understanding the genetic basis of virulence and drug resistance. [See the news story by Pennisi.]

  14. Metabolism and Self-Control

    Amino acid biosynthesis is a basic metabolic process that requires tight regulation in response to changing environmental and cellular conditions. Studies in bacteria and yeast have revealed intriguing control mechanisms, but little work has been performed with plants. Chiba et al. (p. 1371) used genetics to examine methionine (Met) biosynthesis in Arabidopsis. Cystathionine γ-synthase, a key enzyme in Met biosynthesis, was shown to destabilize its own messenger RNA in response to excess Met. This mechanism may be similar to that used in the control of a β-tubulin gene in animal cells.

  15. A Role of its Own

    The p44 mitogen-activated protein kinase (MAPK) and its isoform, p42 MAPK, participate in signaling in response to many different stimuli in a broad range of cell types, and it has not been clear whether each has specific functions or whether the two enzymes can compensate for one another. Pagès et al. (p. 1374) describe the phenotype of mice lacking the p44 mitogen-activated protein kinase. Mice lacking p44 MAPK were viable and fertile, but had specific defects in maturation and proliferation of thymocytes. Although p44 MAPK is not an essential protein for life (probably because the remaining p42 MAPK prevents complete loss of function), it appears to have a distinct biological role in the development of the immune system.

  16. BACE2, a Homolog of BACE, in the Down Syndrome Region of Chromosome 21

    Vassar et al. (Research Articles, 22 October, p. 735) identified and characterized BACE, a transmembrane aspartyl protease with b-secretase activity that cleaves the amyloid precursor protein (APP). One of the products released is the 39- to 43-amino acid amyloid b peptide (Ab), a key component of the brain plaques that are the hallmark of Alzheimer's disease (AD). The identification of an AD-specific b-secretase may lead to the development of inhibitors of this protease to treat this disease.

    Saunders et al. now extend this work by determining the chromosomal localization of BACE. They identified four expressed sequence tags (AI290317, AF150387, R55298, and H60581) that are identical in amino acid sequence to BACE. R55298 has been previously mapped to chromosome 11q23.2-11q23.3, and the investigators mapped H60581 to centimorgan position 121.037 on the summary map for chromosome 11. Separately, Fan et al. also localized BACE to chromosome 11q23.3 by radiation hybrid analyses. Saunders et al. searched the Genbank database and retrieved the sequence for complementary DNAs (AF050171, AF117892) that encode a BACE homolog (BACE2) located on chromosome 21q22.3. BACE and BACE2 exhibit 52% amino acid sequence identity and 68% similarity. BACE2 contains two aspartyl protease active sites at similar positions to those in BACE, which suggests that BACE2 is also a putative β-secretase. In response, Fan et al. report that experiments using BACE antisense oligonucleotides in HEK 293 cells suggest that BACE2 is unlikely to be the principal β-secretase, at least not in these cells.

    Of added interest, BACE2 maps to the obligatory Down syndrome (DS; trisomy 21) region. Thus, in addition to the contribution of an additional copy of the APP gene in DS patients, the chromosomal localization of BACE2 suggests that enhanced β-secretase activity may also contribute to the elevated generation of Aβ and its abundant deposition in the brains of middle-aged DS patients. The full text of these comments can be seen at www.sciencemag.org/cgi/content/full/286/5443/1255a

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