Receptor-mediated exopolysaccharide perception controls bacterial infection.

Surface polysaccharides are important for bacterial interactions with multicellular organisms, and some are virulence factors in pathogens. In the legume-rhizobium symbiosis, bacterial exopolysaccharides (EPS) are essential for the development of infected root nodules. We have identified a gene in Lotus japonicus, Epr3, encoding a receptor-like kinase that controls this infection. We show that epr3 mutants are defective in perception of purified EPS, and that EPR3 binds EPS directly and distinguishes compatible and incompatible EPS in bacterial competition studies. Expression of Epr3 in epidermal cells within the susceptible root zone shows that the protein is involved in bacterial entry, while rhizobial and plant mutant studies suggest that Epr3 regulates bacterial passage through the plant's epidermal cell layer. Finally, we show that Epr3 expression is inducible and dependent on host perception of bacterial nodulation (Nod) factors. Plant-bacterial compatibility and bacterial access to legume roots is thus regulated by a two-stage mechanism involving sequential receptor-mediated recognition of Nod factor and EPS signals.

Level of evidence used in recommendations by the National Comprehensive Cancer Network (NCCN) guidelines beyond Food and Drug Administration approvals.

BACKGROUND: A previous analysis of 113 National Comprehensive Cancer Network® (NCCN®) recommendations reported that NCCN frequently recommends beyond Food and Drug Administration (FDA)-approved indications (44 off-label recommendations) and claimed that the evidence for these recommendations was weak. METHODS: In order to determine the strength of the evidence, we carried out an in-depth re-analysis of the 44 off-label recommendations listed in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). RESULTS: Of the 44 off-label recommendations, 14 were later approved by the FDA and/or are supported by randomized controlled trial (RCT) data. In addition, 13 recommendations were either very minor extrapolations from the FDA label (n = 8) or were actually on-label (n = 5). Of the 17 remaining extrapolations, 8 were for mechanism-based agents applied in rare cancers or subsets with few available treatment options (median response rate = 43%), 7 were based on non-RCT data showing significant efficacy (>50% response rates), and 2 were later removed from the NCCN Guidelines because newer therapies with better activity and/or safety became available. CONCLUSION: Off-label drug use is a frequent component of care for patients with cancer in the United States. Our findings indicate that when the NCCN recommends beyond the FDA-approved indications, the strength of the evidence supporting such recommendations is robust, with a significant subset of these drugs later becoming FDA approved or supported by RCT. Recommendations without RCT data are often for mechanism-based drugs with high response rates in rare cancers or subsets without effective therapies.

A dynamic upper atmosphere of Venus as revealed by VIRTIS on Venus Express.

The upper atmosphere of a planet is a transition region in which energy is transferred between the deeper atmosphere and outer space. Molecular emissions from the upper atmosphere (90-120 km altitude) of Venus can be used to investigate the energetics and to trace the circulation of this hitherto little-studied region. Previous spacecraft and ground-based observations of infrared emission from CO2, O2 and NO have established that photochemical and dynamic activity controls the structure of the upper atmosphere of Venus. These data, however, have left unresolved the precise altitude of the emission owing to a lack of data and of an adequate observing geometry. Here we report measurements of day-side CO2 non-local thermodynamic equilibrium emission at 4.3 microm, extending from 90 to 120 km altitude, and of night-side O2 emission extending from 95 to 100 km. The CO2 emission peak occurs at approximately 115 km and varies with solar zenith angle over a range of approximately 10 km. This confirms previous modelling, and permits the beginning of a systematic study of the variability of the emission. The O2 peak emission happens at 96 km +/- 1 km, which is consistent with three-body recombination of oxygen atoms transported from the day side by a global thermospheric sub-solar to anti-solar circulation, as previously predicted.

South-polar features on Venus similar to those near the north pole.

Venus has no seasons, slow rotation and a very massive atmosphere, which is mainly carbon dioxide with clouds primarily of sulphuric acid droplets. Infrared observations by previous missions to Venus revealed a bright 'dipole' feature surrounded by a cold 'collar' at its north pole. The polar dipole is a 'double-eye' feature at the centre of a vast vortex that rotates around the pole, and is possibly associated with rapid downwelling. The polar cold collar is a wide, shallow river of cold air that circulates around the polar vortex. One outstanding question has been whether the global circulation was symmetric, such that a dipole feature existed at the south pole. Here we report observations of Venus' south-polar region, where we have seen clouds with morphology much like those around the north pole, but rotating somewhat faster than the northern dipole. The vortex may extend down to the lower cloud layers that lie at about 50 km height and perhaps deeper. The spectroscopic properties of the clouds around the south pole are compatible with a sulphuric acid composition.

Chemical composition of lipopolysaccharides isolated from various endophytic nitrogen-fixing bacteria of the genus Herbaspirillum.

Bacteria from the genus Herbaspirillum are endophytes responsible for nitrogen fixation in gramineous plants of economic importance such as maize, sugarcane, sorghum, rice, and wheat. Some species are known to produce plant growth substances. In contrast, Herbaspirillum rubrisubalbicans strains are known to be mild plant pathogens. The molecular communication between the plant and the microbes might involve lipopolysaccharides present in the outer membrane of these gram-negative bacteria. Phenol-water extraction was used to obtain lipopolysaccharides from 7 strains of Herbaspirillum seropedicae (SmR1, Z67, Z78, ZA95, and M2) and H. rubrisubalbicans (M1 and M4). The electrophoretic profiles and chemical composition of the lipopolysaccharides obtained in the phenol and aqueous extracts were shown herein.

A tenuous carbon dioxide atmosphere on Jupiter's moon Callisto.

An off-limb scan of Callisto was conducted by the Galileo near-infrared mapping spectrometer to search for a carbon dioxide atmosphere. Airglow in the carbon dioxide nu3 band was observed up to 100 kilometers above the surface and indicates the presence of a tenuous carbon dioxide atmosphere with surface pressure of 7.5 x 10(-12) bar and a temperature of about 150 kelvin, close to the surface temperature. A lifetime on the order of 4 years is suggested, based on photoionization and magnetospheric sweeping. Either the atmosphere is transient and was formed recently or some process is currently supplying carbon dioxide to the atmosphere.

Pioneer 10 observations of the ultraviolet glow in the vicinity of jupiter.

A two-channel ultraviolet photometer aboard Pioneer 10 has made several observations of the ultraviolet glow in the wavelength range from 170 to 1400 angstroms in the vicinity of Jupiter. Preliminary results indicate a Jovian hydrogen (1216 angstrom) glow with a brightness of about 1000 rayleighs and a helium (584 angstrom) glow with a brightness of about 10 to 20 rayleighs. In addition, Jupiter appears to have an extensive hydrogen torus surrounding it in the orbital plane of Io. The mean diameter of the torus is about equal to the diameter of the orbit of Io. Several observations of the Galilean satellites have also occurred but only a rather striking Io observation has been analyzed to date. If the observed Io glow is predominantly that of Lyman-alpha, the surface brightness is about 10,000 rayleighs.

Ultraviolet photometer observations of the saturnian system.

Several interesting cloud and atmospheric features of the Saturn system have been observed by the long-wavelength channel of the two-channel ultraviolet photometer aboard the Pioneer Saturn spacecraft. Reported are observations of the most obvious features, including a Titan-associated cloud, a ring cloud, and the variation of atmospheric emission across Saturn's disk. The long-wavelength data for Titan suggest that a cloud of atomic hydrogen extends at least 5 Saturn radii along its orbit and about 1.5 Saturn radii vertically. A ring cloud, thought to be atomic hydrogen, has also been observed by the long-wavelength channel of the photometer; it shows significant enhancement in the vicinity of the B ring. Finally, spatially resolved observations of Saturn's disk show significant latitudinal variation. Possible explanations of the variation include aurora or limb brightening.

Sulfuric acid on Europa and the radiolytic sulfur cycle.

A comparison of laboratory spectra with Galileo data indicates that hydrated sulfuric acid is present and is a major component of Europa's surface. In addition, this moon's visually dark surface material, which spatially correlates with the sulfuric acid concentration, is identified as radiolytically altered sulfur polymers. Radiolysis of the surface by magnetospheric plasma bombardment continuously cycles sulfur between three forms: sulfuric acid, sulfur dioxide, and sulfur polymers, with sulfuric acid being about 50 times as abundant as the other forms. Enhanced sulfuric acid concentrations are found in Europa's geologically young terrains, suggesting that low-temperature, liquid sulfuric acid may influence geological processes.

Images of Io's Sodium Cloud.

The first direct images of Io's sodium cloud are reported and analyzed. The observed cloud extends for more than 10(5) kilometers along Io's orbit and is a somewhat "banana-shaped" partial toroid. More sodium atoms precede Io than follow it. A model based on the escape of sodium from a specific localized area on Io provides a reasonable fit to the observed intensity distribution whereas isotropic escape does not.

The early evolution of the inner solar system: a meteoritic perspective.

Formation of the solar system may have been triggered by a stellar wind. From then on, the solar system would have followed a conventional evolutionary path, including the formation of a disk and bipolar jets. The now extinct short-lived radionuclides beryllium-10 and, possibly, manganese-53 that were present in meteorites probably resulted from energetic particle irradiation within the solar system. Calcium-aluminum-rich inclusions (the oldest known solar system solids) and chondrules could have been produced by the bipolar jets, but it is more likely that they formed during localized events in the asteroid belt. The chondritic meteorites formed within the temperature range (100 to 400 kelvin) inferred for the midplane of classical T Tauri disks at 2 to 3 astronomical units from their central stars. However, these meteorites may retain a chemical memory of earlier times when midplane temperatures were much higher. Dissipation of the solar nebula occurred within a few million years of solar system formation, whereas differentiation of asteroidal-sized bodies occurred within 5 to 15 million years. The terrestrial planets took approximately 100 million years to form. Consequently, they would have accreted already differentiated bodies, and their final assembly was not completed until after the solar nebula had dispersed. This implies that water-bearing asteroids and/or icy planetesimals that formed near Jupiter are the likely sources of Earth's water.

Isotopic tracking of change in diet and habitat use in african elephants.

The carbon, nitrogen, and strontium isotope compositions of elephants in Amboseli Park, Kenya, were measured to examine changes in diet and habitat use since the 1960s. Carbon isotope ratios, which reflect the photosynthetic pathway of food plants, record a shift in diet from trees and shrubs to grass. Strontium isotope ratios, which reflect the geologic age of bedrock, document the concentration of elephants within the park. The high isotopic variability produced by behavioral and ecological shifts, if it is representative of other East African elephant populations, may complicate the use of isotopes as indicators of the source region of ivory.

An Atmosphere on Ganymede from Its Occultation of SAO 186800 on 7 June 1972.

On 7 June 1972 the third , Jovian satellite Ganymede occulted the eighth-magnitude star SAO 186800. Successful photoelectric observations obtained at Lembang, Java (Indonesia), and Kavalur, India, show nonabrupt immersions and emersions, indicating the presence of an atmosphere whose surface pressure is greater than about 10(-3) millibar. By fitting the two occultation durations as chords to a model disk, the diameter is found to be 5270 (+30, - approximately 200) kilometers, the major error contribution arising from the uncertain atmospheric thickness below the occultation layer. The derived mean density is 2.0 (-0.03, + approximately 0.2) grams per cubic centimeter.

Rhenium-osmium and samarium-neodymium isotopic systematics of the stillwater complex.

Isotopic data for the Stillwater Complex, Montana, which formed about 2700 Ma (million years ago), were obtained to evaluate the role of magma mixing in the formation of strategic platinum-group element (PGE) ore deposits. Neodymium and osmium isotopic data indicate that the intrusion formed from at least two geochemically distinct magmas. Ultramafic affinity (U-type) magmas had initial epsilon(Nd) of -0.8 to -3.2 and a chondritic initial (187)Os/(186)Os ratio of approximately 0.88, whereas anorthositic affinity (A-type) magmas had epsilon(Nd) of -0.7 to +1.7 and an initial (187)Os/(186)Os ratio of approximately -1.13. These data suggest that U-type magmas were derived from a lithospheric mantle source containing recycled crustal materials whereas A-type magmas originated either by crustal contamination of basaltic magmas or by partial melting of basalt in the lower crust. The Nd and Os isotopic data also suggest that Os, and probably the other PGEs in ore horizons such as the J-M Reef, was derived from A-type magmas. The Nd and Os isotopic heterogeneity observed in rocks below the J-M Reef also suggests that A-type magmas were injected into the Stillwater U-type magma chamber at several stages during the development of the Ultramafic series.

Organics and other molecules in the surfaces of Callisto and Ganymede.

Five absorption features are reported at wavelengths of 3.4, 3.88, 4. 05, 4.25, and 4.57 micrometers in the surface materials of the Galilean satellites Callisto and Ganymede from analysis of reflectance spectra returned by the Galileo mission near-infrared mapping spectrometer. Candidate materials include CO2, organic materials (such as tholins containing C(triple bond)N and C-H), SO2, and compounds containing an SH-functional group; CO2, SO2, and perhaps cyanogen [(CN)2] may be present within the surface material itself as collections of a few molecules each. The spectra indicate that the primary surface constituents are water ice and hydrated minerals.

Salts on Europa's surface detected by Galileo's near infrared mapping spectrometer. The NIMS Team.

Reflectance spectra in the 1- to 2.5-micrometer wavelength region of the surface of Europa obtained by Galileo's Near Infrared Mapping Spectrometer exhibit distorted water absorption bands that indicate the presence of hydrated minerals. The laboratory spectra of hydrated salt minerals such as magnesium sulfates and sodium carbonates and mixtures of these minerals provide a close match to the Europa spectra. The distorted bands are only observed in the optically darker areas of Europa, including the lineaments, and may represent evaporite deposits formed by water, rich in dissolved salts, reaching the surface from a water-rich layer underlying an ice crust.

A close-up look at Io from Galileo's near-infrared mapping spectrometer.

Infrared spectral images of Jupiter's volcanic moon Io, acquired during the October and November 1999 and February 2000 flybys of the Galileo spacecraft, were used to study the thermal structure and sulfur dioxide distribution of active volcanoes. Loki Patera, the solar system's most powerful known volcano, exhibits large expanses of dark, cooling lava on its caldera floor. Prometheus, the site of long-lived plume activity, has two major areas of thermal emission, which support ideas of plume migration. Sulfur dioxide deposits were mapped at local scales and show a more complex relationship to surface colors than previously thought, indicating the presence of other sulfur compounds.

Hydrogen peroxide on the surface of Europa.

Spatially resolved infrared and ultraviolet wavelength spectra of Europa's leading, anti-jovian quadrant observed from the Galileo spacecraft show absorption features resulting from hydrogen peroxide. Comparisons with laboratory measurements indicate surface hydrogen peroxide concentrations of about 0.13 percent, by number, relative to water ice. The inferred abundance is consistent with radiolytic production of hydrogen peroxide by intense energetic particle bombardment and demonstrates that Europa's surface chemistry is dominated by radiolysis.

Galileo infrared imaging spectroscopy measurements at venus.

During the 1990 Galileo Venus flyby, the Near Infaied Mapping Spectrometer investigated the night-side atmosphere of Venus in the spectral range 0.7 to 5.2 micrometers. Multispectral images at high spatial resolution indicate substanmial cloud opacity variations in the lower cloud levels, centered at 50 kilometers altitude. Zonal and meridional winds were derived for this level and are consistent with motion of the upper branch of a Hadley cell. Northern and southern hemisphere clouds appear to be markedly different. Spectral profiles were used to derive lower atmosphere abundances of water vapor and other species.

Enhancement of the clinical activity of melphalan by the hypoxic cell sensitizer misonidazole.

One hundred patients with non-small cell lung cancer were entered by members of the Northern California Oncology Group into a randomized Phase II trial of i.v. melphalan versus i.v. melphalan with concomitant oral misonidazole. The patients had not received prior chemotherapy. Eighty-five patients were evaluable for assessment of response and 89 were evaluable for toxicity analysis. The melphalan/misonidazole group had a superior response rate (two complete and four partial responses among 42 patients or 14%) compared to the melphalan group in which there were no responses among 43 patients (p = 0.024, two-sided Fisher exact test). Since hematological toxicity was equivalent in the two groups, there was an improvement in therapeutic index. Data from 12 patients undergoing pharmacological studies demonstrated that the plasma concentration of melphalan was 25% higher in the misonidazole group, a difference that is not statistically significant. Although the mechanism of interaction has not been fully established, this randomized trial demonstrates that a chemosensitizer can enhance the clinical antitumor activity of an alkylating agent and suggests that chemosensitizers in combination with alkylating agents should be investigated in further clinical trials.