By reducing the enzyme expression of the rpd3 histone deacetylase in Drosophila, Rogina et al. (p. 1745) show that an increase of 33% to 54% results in their normal life-span similar to the increases seen in yeast mutants.
How Does Your Planet Grow?
To date, the detection of about 100 giant gaseous planets orbiting nearby stars would suggest that such planets are relatively common. However, simulations that try to account for their formation often run into difficulties in condensing the objects or, once they have formed, of not shearing them apart through tidal forces. Mayer et al. (p. 1756; see the news story by Kerr) have now performed higher resolution smoothed-particle hydrodynamic simulations to show that giant planets can form through gravitational instabilities in relatively cool protoplanetary disks over short time scales (about 1000 years).
Martian Meteorites Can Escape
Simulations of ejecta velocities from bolide impacts onto Mars have not been easy to correlate with the number and characteristics of the known martian meteorites found on Earth. Head et al. (p. 1752) have performed higher resolution simulations that show that the velocities of the spallated material can exceed the escape velocity for Mars. Craters as small as 3 kilometers in diameter can launch about 100 decimeter-sized fragments into interplanetary space. The small number of these fragments that have a high probability of reaching Earth are consistent with the currently observed meteorite collection corrected for the estimated sampling bias. The simulations also show that older martian terrains covered by a blanket of thicker regolith will require larger bolides (and thus larger craters) to eject martian bedrock into space.
Harnessing Nanoparticles in Vivo
Fluorescent semiconductor nanocrystals, or quantum dots (QDs), could be ideal markers for biological studies because they photobleach much more slowly than do dye molecules and their emission wavelength can be finely tuned. However, the QDs must first be encapsulated with a biocompatible layer to improve their solubility while maintaining their stability and fluorescence and avoiding nonspecific adsorption. Dubertret et al. (p. 1759) encapsulated CdSe QDs with a phospholipid block copolymer and show that when conjugated to DNA, the coated QDs can be used as in vitro probes to highlight specific complementary sequences. A lineage-tracing study of Xenopus embryos shows that the QDs have low cell migration and low toxicity.
The properties of some crystals can be modified by intercalation of molecular species to form a host-guest framework. Halder et al. (p. 1762; see the Perspective by Turnbull and Landee) modified a framework based on an iron(II) complex by adding ethanol guest molecules. The pure framework does not show any magnetic transitions on cooling, but the guest-complexed crystal exhibits a spin-crossover in which half of the iron sites change from a high to low spin state.
The deep ocean was colder and saltier during the Last Glacial Maximum (LGM) than it is today, and these differences affected thermohaline circulation. Adkins et al. (p. 1769; see the Perspective by Boyle) created a temperature and salinity “map” of the LGM deep ocean by analyzing the chloride concentration and oxygen isotope ratios of fluids trapped in deep-sea sediments from the Atlantic, Pacific, and Southern Ocean basins. The Southern Ocean was the saltiest water mass during the glacial period, the reverse of the modern Atlantic salinity gradient. Thermohaline circulation was dominated by variations in salinity during the LGM, as opposed to present conditions, where temperature is the main variable.
The formation of a new species is generally thought to be gradual and to require isolation. Greig et al. (p. 1773) show experimentally that speciation can occur rapidly after hybridization of yeast species. Although most of the hybrids were infertile, the vast populations that could be created with yeast allowed viable hybrid spores to be collected. Subsequent generations of hybrids had variable but increasing fertility, and showed a spectrum of growth temperature optima that depended on the parental phenotype and contribution to the offsprings' genomes. The authors suggest that the reproductive isolation seen among the different generations and with their parents originates in different combinations of gene and chromosomal incompatibilities acting across the generations. In the wild, the fitness of yeast hybrids may be compromised so much by environmental conditions that speciation is curtailed.
The Whens and Wheres of Neural Expression
For normal organ and tissue development and function, certain genes must be expressed at the appropriate place and time. For example, neural genes must be expressed in neural tissue but shut down in nonneural tissues. Lunyak et al. (p. 1747) examined mechanisms by which neural-specific gene expression can be restricted from nonneural tissues. The zinc-finger transcription factor REST/NRSF can mediate extraneural restriction through two different mechanisms, one of which uses active repression via a histone deacetylation complex and one that involves gene silencing via DNA methylation and the recruitment of the corepressor CoREST and silencing machinery. The latter mechanism can mediate gene silencing of specific chromosomal regions, including gene clusters encompassing neuron-specific genes, some of which do not themselves contain REST/NRSF response elements.
A family of RNA-protein complexes, known as the uridine-rich small nuclear ribonucleoproteins (U snRNPs), form the core of the spliceosome that excises introns and ligates exons to form messenger RNA. A functional deficiency in the survival of motor neurons (SMN) protein results in spinal muscular atrophy, a disease in which motor neurons of the spinal cord degenerate. Pellizzoni et al. (p. 1775) show that the SMN complex (of which the SMN protein is a part) serves to assemble in an orderly fashion the protein ingredients of U snRNPs (the Sm proteins) onto the U snRNAs. It first binds the Sm proteins, then the U snRNAs, and finally puts them together in an adenosine-triphosphate (ATP-dependent) reaction.
Neurotrypsin and Mental Retardation
Inherited mental retardation (MR) is often linked to abnormalities on the X chromosome or to abnormalities in brain development or other clinically identifiable features, but in most cases none of these attributes are present. An analysis of such nonsyndromic MR patients by Molinari et al. (p. 1779) revealed an association with the mutation of the serine protease neurotrypsin. In situ hybridization studies of the expression of neurotrypsin during normal development revealed that it is expressed in parts of the brain associated with learning and memory and first appears at 44 days of development. Immunoelectron microscopy localized neurotrypsin at presynaptic nerve endings. Although this mutation does not appear to be a common cause of MR, further studies may yield insights into the pathways leading to these diseases.
Neurotoxic, Cytosolic Prion Proteins
The characteristics of the prion protein, which has been linked to a variety of neurodegenerative disorders, is the subject of two reports. Ma and Lindquist (p. 1785) reveal how inhibition of the proteasome machinery in cells that produce prion proteins can lead to the accumulation of prion isoforms in the cytosol, and how, under certain conditions, misfolded self-perpetuating isoforms can be generated de novo. Ma et al. (p. 1781) examined the effects of retrograde-transported or cytosolically expressed prion protein in a transgenic mouse model and in neuronal cell lines. Cytosolic prion protein was highly neurotoxic, and mice engineered to possess cytosolic prion protein developed severe ataxia, cerebellar degeneration, and gliosis.
The Hydrogen Economy of the Gut
A major cause of gastritis, peptic ulcers, and certain cancers is the bacterium Helicobacter pylori. Olson and Maier (p. 1788) show that the colonization success of this common pathogen is boosted by hydrogen gas produced by other intestinal occupants. Molecular hydrogen in the mucous lining of the stomach stimulates the pathogen to produce more of a constitutive enzyme, hydrogenase, required to harvest the energy through a series of heme-containing electron carriers.
Glycosylation in Bacteria
N-linked glycosylation is a common posttranslational modification of membrane and secretory proteins in eukaryotes. However, the only bacterium known to modify proteins in this way is Campylobacter jejuni, and thus many eukaryotic proteins generated in bacterial systems are of limited use because they lack appropriate modifications. Wacker et al. (p. 1790) have transplanted the N-linked glycosylation machinery from C. jejuni to Escherichia coli, which should enhance the opportunities for the large-scale production of appropriately modified proteins in bioreactors.
Mid-ocean ridges are usually modeled as propagating fractures in a linear elastic medium, even though the rifting occurs in the brittle crust. Floyd et al. (p. 1765; see the cover) observed seismicity related to rift propagation along the Galapagos Rise in Hess Deep using six autonomous hydrophones moored in the eastern equatorial Pacific Ocean. The seismic events were concentrated in space and time along the tip of the rift, and this finding is consistent with laboratory-based acoustic emission tests which show that crack growth is controlled by a sequence of microcracks that coalescence into one propagating fracture. At the Galapagos Rise, microfractures are concentrated at the rift tip under low tensile stress and then coalescence into a larger fracture, showing that rifts can propagate in a stable fashion in the brittle crust.
Degrading the Signal Lipids
Endocannabinoid-signaling lipids bind to the cannabinoid receptor and modulate behaviors such as pain and cognition. Their activity is terminated when the lipids are degraded by the integral membrane protein fatty acid amide hydrolase (FAAH). Now Bracey et al. (p. 1793) have determined the structure of FAAH bound to an inhibitor at 2.8 angstrom resolution. The structure is similar to soluble hydrolases in the same family, but key differences allow integration into membranes and create a binding pocket for the hydrophobic substrate. The active site is near the membrane surface and has direct access both to the lipid bilayer and the cytoplasm so that signaling lipids can enter the active site from the membrane, and polar amine products could exit into the cytoplasm.
Variation in the ability to cope with infection among individuals helps ensure the success of a given population. Extensive polymorphism in the genes of the major histocompatibility complex (MHC) are consistent with control of resistance, either through the presentation of different foreign peptides by MHC proteins, the selection of distinct repertoires of T cells during development, or through both processes. Messaoudi et al. (p. 1797) observed a large divergence in the response to viral infection in two strains of mice carrying a four-amino acid difference in one MHC gene, but which were otherwise genetically identical. T cells in both strains focused on the same dominant viral peptide, which bound with equal affinity to each MHC variant. However, T cells responsible for better viral clearance in the resistant strain showed greater diversity of T cell receptor usage and improved recognition of antigen. Thus, MHC polymorphism may influence different responses to infection through the repertoire of T cells they select.