This Week in Science

Science  18 Jul 1997:
Vol. 277, Issue 5324, pp. 289
  1. Structural clues to Ras activation

    The small guanosine triphosphatase (GTPase) Ras is a critical component of signaling pathways that control cell growth, and oncogenic mutations of Ras are found in many human tumors. Inactivation of Ras requires hydrolysis of bound GTP to guanosine diphosphate (GDP), a reaction that is stimulated by proteins called GAPs (GTPase-activating proteins). Scheffzek et al. (p. 333; see the cover and the Perspective by Sprang, p. 329) present the three-dimensional crystal structure of human H-Ras-GDP bound to the GTPase-activating domain of the GAP known as p120GAP. The structure reveals the mechanism by which GAP enhances hydrolysis of GTP by Ras. Analysis of the structure shows why oncogenic mutations of Ras are insensitive to GAP and thus remain in an active state that leads to uncontrolled cell growth.

  2. Too hot to handle easily

    At high temperatures, the spectra of water and other molecules can no longer be interpreted by using standard perturbation methods for spectroscopic analysis, which can present problems, for example, in assigning astronomical spectra. Polyansky et al. (p. 346; see the Perspective by Oka, p. 328) show that by using an accurate variational method, hot water spectra, such as those that have been observed for water in a sunspot, can be assigned with high accuracy and allow the identification of many previously unidentified bands.

  3. Europa's tenuous ionosphere

    The Galileo spacecraft, on its tour of the jovian system, has also been used in three occultations with Europa, the second Galilean satellite orbiting Jupiter, to look for any signs of an atmosphere around the satellite. Kliore et al. (p. 355) measured a tenuous ionosphere that they believe to be produced by particle impact on Europa's water ice surface. If the atmosphere is rich in O2 or H2O, then the atmospheric temperature may be as high as 340 kelvin, much higher than the icy surface. Thus, the satellite's atmosphere may be externally heated by Jupiter's magnetosphere.

  4. Invisible polar wind

    The polar wind is the outflow of plasma along magnetic field lines from Earth's poles into the near-Earth plasma sheet (the magnetosphere). The low density of ions in the polar wind has made it difficult to measure their distribution and origin, but the POLAR spacecraft, which orbits the poles, has overcome that difficulty with a specially designed plasma ion counter. Moore et al. (p. 349) have found that O+ is more abundant and has a higher flux rate and temperature than was predicted. These measurements will require re-analysis of the models used to understand the origin of the plasma flow into the magnetosphere and its effects on magnetospheric storms and auroras.

  5. Forget not the south

    The pattern of increases in surface air temperatures during the last century provide information on the relative effects of different causes—such as an increase in greenhouse gases and the effects of aerosols, volcanic eruptions, and increased urbanization. Easterling et al. (p. 364) expand the analysis of trends in minimum and maximum daily temperatures by including records from much of the Southern Hemisphere. The analysis shows that the daily range in temperatures (maximum minus minimum) decreased from 1950 to 1993, primarily because minimum temperatures have risen faster than maximum ones. The data also imply that urbanization has had a minimal effect on the temperature records.

  6. Prion-like propagation in yeast

    Prions are thought to be proteins that take on an abnormal conformation which they can then confer onto other molecules of the same type that are in a normal conformation. Such propagation of a pathogenic conformation of certain proteins appears to cause diseases in man and other animals. Yeast have a protein known as Sup35 that participates in termination of translation and behaves genetically like a prion. Paushkin et al. (p. 381; see the news story by Vogel, p. 314) report that the altered conformational form of Sup35 can be propagated in vitro through several cycles. The results show similarities of prion characteristics from yeast and mammals and support the “protein only” hypothesis for propagation of such agents.

  7. A daughter's message

    How do cells acquire distinct phenotypes after cell division? One well-studied example occurs in yeast, where mother cells are distinguished from daughter cells by their ability to switch mating types. At the molecular level, this difference is due to selective transcription of the HO endonuclease in mother cells, which in turn is due to selective accumulation of a transcriptional repressor of HO, Ash1p, in daughter cells. Long et al. (p. 383) now show that the accumulation of Ash1p protein arises because Ash1p messenger RNA is asymmetrically distributed to daughter cells. Until now, asymmetric messenger RNA distribution has been observed only in cells of higher eukaryotes, so these observations with yeast suggest that this mechanism of gene regulation may have ancient origins.

  8. Apoptosis and Alzheimer's

    Evidence from a variety of sources has linked apoptosis (programmed cell death) to Alzheimer's disease. Early onset familial Alzheimer's disease is associated with mutations in presenilins 1 and 2 (PS1 and PS2). If apoptosis is induced in neuroblastoma and neuroglioma cell lines or if PS1 and PS2 are overexpressed, these genes are cleaved at unusual sites. Kim et al. (p. 373) have shown that this alternative cleavage can be blocked by inhibitors of the caspase-3 family of proteases. Higher levels of the abnormal products were found in cells expressing the mutant forms of PS1 and PS2. These abnormal cleavage products could, in turn, make cells more susceptible to apoptosis or could increase production of amyloid precursors that would promote apoptosis and thus lead to the pathology of Alzheimer's disease.

  9. Shocking crystallization

    Meteorites experienced shock-induced high pressures and temperatures when they were ejected from their parent bodies by an impact. Sharp et al. analyzed the shock-induced melt veins in Acfer 040, an ordinary chondrite that was found in the Sahara. Transmission electron microscopy and x-ray diffraction studies of grains in these veins indicate the occurrence of MgSiO3-ilmenite. MgSiO3-ilmenite has not been observed in any natural specimens, and it not among the predicted liquidus phases for typical Earth-like starting compositions. The authors suggest this phase was formed at high pressure (>25 gigapascals) during the impact event and may represent an analog of a so far unobserved phase of Earth's lower mantle.

  10. Sulfur in the solar nebula

    Chondrites, meteorites filled with chondrules that are assumed to represent condensates from the earliest formed components of the solar nebula, also contain ubiquitous sulfide minerals. Lauretta et al. synthesized sulfides with similar morphologies and composition as some chondritic sulfides by placing a solar composition Fe-Ni alloy in a hydrogen sulfide-rich gas. They suggest that some chondritic sulfides may be condensates from the solar nebula and can thus be used as tracers of the temperature in the nebula when these phases formed.

  11. Waters running deep

    Ocean circulation in deeper water layers is much less understood than that in layers nearer to the surface, which leads to uncertainties in the overall understanding of ocean circulation patterns. Lozier analyzed data from a recently compiled database of ocean circulation and shows that a deep water circulation pattern exists in the North Atlantic that is dissociated from the wind-driven surface layer circulations. These recirculation patterns are likely to affect the distribution of climatic anomalies and should therefore be taken into account in modeling studies.

  12. Blocking and entering

    Polyketides include a number of important drand the need for new drug candidates, such as for combating resistance, has led to efforts to modify polyketide synthase (PKS) pathways. Jacobsen et al. show that molecules, both natural and synthetic, can be introduced into an in vivo PKS pathway. They blocked the first condensation step performed by 6-deoxyerythronolide B synthase, which synthesizes the parent molecule for erythromycin. They could then introduce cell-permeable N-acetylcysteamine thioesters into the pathway, which were accepted as substrates for subsequent steps. Some unusual incorporation patterns were seen, which suggests that this approach could be used to make a diverse range of compounds. [See the news story by Service.

  13. Insights from CD1's structure

    The antigen-presenting molecule CD1 represents a family of molecules that are distantly related to the major histocompatibility complex (MHC) molecules of the immune system. Zeng et al. crystallized CD1 and showed by sequence and structure comparison that it is both related to and divergent from MHC class I and class II complexes. The structure is unusual in that the region corresponding to the peptide binding groove is larger and has greater hydrophobicity and fewer polar and charged groups. The shape and hydrophobicity of the binding groove of CD1 is consistent with observations that human CD1b and CD1c can present mycobacterial cell wall antigens such as mycolic acid and lipoarabinomannans (a lipopolysaccharide category), thus accounting for the versatility of the antigen presentation system. [See the Perspective by Brenner.]

  14. Channels to cell death

    The cell is equipped with molecules that can induce cell death (apoptosis) or that can promote survival. The Bcl-2 family of proteins contains members that do both. Antonsson et al. found that the pro-death protein Bax can form pH- and voltage-dependent channels in planar membranes and can cause the death of neurons when applied exogenously in culture. Both of these properties can be inhibited by the addition of Bcl-2, an anti-apoptotic protein, to the assay. The channels formed by Bax are functional at physiologic pH, unlike those of Bcl-2. Because these proteins can be found in the mitochondria, and the mitochondria are critical to apoptosis, the possibility exists that channel formation may be important in regulating cell death.

  15. Knowing and doing

    A fundamental separation in human memory systems lies between declarative (fact- and event-based) and procedural (learned abilities). Whether semantic (fact) and episodic (event) memories are localized to distinct anatomical systems has been unclear. Vargha-Khadem et al. present three patients who suffered bilateral hippocampal damage early in life yet have learned to read and to write with reasonable proficiency. It appears that a substantial contribution to their literacy comes from residual semantic memory, which must have continued to function despite their hippocampal amnesia as evidenced by their inability to recall quotidian events such as dates and conversations. [See the Perspective by Eichenbaum.

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