Rapid pneumococcal evolution in response to clinical interventions

Epidemiological studies of the naturally transformable bacterial pathogen Streptococcus pneumoniae have previously been confounded by high rates of recombination. Sequencing 240 isolates of the PMEN1 (Spain(23F)-1) multidrug-resistant lineage enabled base substitutions to be distinguished from polymorphisms arising through horizontal sequence transfer. More than 700 recombinations were detected, with genes encoding major antigens frequently affected. Among these were 10 capsule-switching events, one of which accompanied a population shift as vaccine-escape serotype 19A isolates emerged in the USA after the introduction of the conjugate polysaccharide vaccine. The evolution of resistance to fluoroquinolones, rifampicin, and macrolides was observed to occur on multiple occasions. This study details how genomic plasticity within lineages of recombinogenic bacteria can permit adaptation to clinical interventions over remarkably short time scales.     

Evidence for a late supernova injection of 60Fe into the protoplanetary disk

High-precision 60Fe-60Ni isotope data show that most meteorites originating from differentiated planetesimals that accreted within 1 million years of the solar system's formation have 60Ni/58Ni ratios that are approximately 25 parts per million lower than samples from Earth, Mars, and chondrite parent bodies. This difference indicates that the oldest solar system planetesimals formed in the absence of 60Fe. Evidence for live 60Fe in younger objects suggests that 60Fe was injected into the protoplanetary disk approximately 1 million years after solar system formation, when 26Al was already homogeneously distributed. Decoupling the first appearance of 26Al and 60Fe constrains the environment where the Sun's formation could have taken place, indicating that it occurred in a dense stellar cluster in association with numerous massive stars.     

Genome-wide insertional mutagenesis of Arabidopsis thaliana

Over 225,000 independent Agrobacterium transferred DNA (T-DNA) insertion events in the genome of the reference plant Arabidopsis thaliana have been created that represent near saturation of the gene space. The precise locations were determined for more than 88,000 T-DNA insertions, which resulted in the identification of mutations in more than 21,700 of the approximately 29,454 predicted Arabidopsis genes. Genome-wide analysis of the distribution of integration events revealed the existence of a large integration site bias at both the chromosome and gene levels. Insertion mutations were identified in genes that are regulated in response to the plant hormone ethylene.     

Mismatch repair, but not heteroduplex rejection, is temporally coupled to DNA replication

In eukaryotes, it is unknown whether mismatch repair (MMR) is temporally coupled to DNA replication and how strand-specific MMR is directed. We fused Saccharomyces cerevisiae MSH6 with cyclins to restrict the availability of the Msh2-Msh6 mismatch recognition complex to either S phase or G2/M phase of the cell cycle. The Msh6-S cyclin fusion was proficient for suppressing mutations at three loci that replicate at mid-S phase, whereas the Msh6-G2/M cyclin fusion was defective. However, the Msh6-G2/M cyclin fusion was functional for MMR at a very late-replicating region of the genome. In contrast, the heteroduplex rejection function of MMR during recombination was partially functional during both S phase and G2/M phase. These results indicate a temporal coupling of MMR, but not heteroduplex rejection, to DNA replication.     

Controlling the charge state of individual gold adatoms

The nature and control of individual metal atoms on insulators are of great importance in emerging atomic-scale technologies. Individual gold atoms on an ultrathin insulating sodium chloride film supported by a copper surface exhibit two different charge states, which are stabilized by the large ionic polarizability of the film. The charge state and associated physical and chemical properties such as diffusion can be controlled by adding or removing a single electron to or from the adatom with a scanning tunneling microscope tip. The simple physical mechanism behind the charge bistability in this case suggests that this is a common phenomenon for adsorbates on polar insulating films.     

Altered telomeres in tumors with ATRX and DAXX mutations

The proteins encoded by ATRX and DAXX participate in chromatin remodeling at telomeres and other genomic sites. Because inactivating mutations of these genes are common in human pancreatic neuroendocrine tumors (PanNETs), we examined the telomere status of these tumors. We found that 61% of PanNETs displayed abnormal telomeres that are characteristic of a telomerase-independent telomere maintenance mechanism termed ALT (alternative lengthening of telomeres). All of the PanNETs exhibiting these abnormal telomeres had ATRX or DAXX mutations or loss of nuclear ATRX or DAXX protein. ATRX mutations also correlate with abnormal telomeres in tumors of the central nervous system. These data suggest that an alternative telomere maintenance function may operate in human tumors with alterations in the ATRX or DAXX genes.     

Enterogastrone inhibits eating by fasted mice

In mice fasted for 17 hours, administration of enterogastrone purified from hog duodenum reduced the food intake. This effect was greatest during the first 30 minutes, but the cumulative reduction continued for at least 4 hours. Other peptides prepared from hog duodenum or colon, as well as glucagon, secretin, glucose, and bovine serum albumin, were ineffective.     

Inhibited and uninhibited infants "grown up": adult amygdalar response to novelty

Infants with an inhibited temperament tend to develop into children who avoid people, objects, and situations that are novel or unfamiliar, whereas uninhibited children spontaneously approach novel persons, objects, and situations. Behavioral and physiological features of these two temperamental categories are moderately stable from infancy into early adolescence and have been hypothesized to be due, in part, to variation in amygdalar responses to novelty. We found that adults who had been categorized in the second year of life as inhibited, compared with those previously categorized as uninhibited, showed greater functional MRI signal response within the amygdala to novel versus familiar faces.     

Advanced technology paths to global climate stability: energy for a greenhouse planet

Stabilizing the carbon dioxide-induced component of climate change is an energy problem. Establishment of a course toward such stabilization will require the development within the coming decades of primary energy sources that do not emit carbon dioxide to the atmosphere, in addition to efforts to reduce end-use energy demand. Mid-century primary power requirements that are free of carbon dioxide emissions could be several times what we now derive from fossil fuels (approximately 10(13) watts), even with improvements in energy efficiency. Here we survey possible future energy sources, evaluated for their capability to supply massive amounts of carbon emission-free energy and for their potential for large-scale commercialization. Possible candidates for primary energy sources include terrestrial solar and wind energy, solar power satellites, biomass, nuclear fission, nuclear fusion, fission-fusion hybrids, and fossil fuels from which carbon has been sequestered. Non-primary power technologies that could contribute to climate stabilization include efficiency improvements, hydrogen production, storage and transport, superconducting global electric grids, and geoengineering. All of these approaches currently have severe deficiencies that limit their ability to stabilize global climate. We conclude that a broad range of intensive research and development is urgently needed to produce technological options that can allow both climate stabilization and economic development.     

Transmission of equine influenza virus to dogs

Molecular and antigenic analyses of three influenza viruses isolated from outbreaks of severe respiratory disease in racing greyhounds revealed that they are closely related to H3N8 equine influenza virus. Phylogenetic analysis indicated that the canine influenza virus genomes form a monophyletic group, consistent with a single interspecies virus transfer. Molecular changes in the hemagglutinin suggested adaptive evolution in the new host. The etiologic role of this virus in respiratory disease was supported by the temporal association of rising antibody titers with disease and by experimental inoculation studies. The geographic expansion of the infection and its persistence for several years indicate efficient transmission of canine influenza virus among greyhounds. Evidence of infection in pet dogs suggests that this infection may also become enzootic in this population.