Structural Insights into Differences in Drug-binding Selectivity between Two Forms of Human α1-Acid Glycoprotein Genetic Variants, the A and F1*S Forms

Human α1-acid glycoprotein (hAGP) in serum functions as a carrier of basic drugs. In most individuals, hAGP exists as a mixture of two genetic variants, the F1*S and A variants, which bind drugs with different selectivities. We prepared a mutant of the A variant, C149R, and showed that its drug-binding properties were indistinguishable from those of the wild type. In this study, we determined the crystal structures of this mutant hAGP alone and complexed with disopyramide (DSP), amitriptyline (AMT), and the nonspecific drug chlorpromazine (CPZ). The crystal structures revealed that the drug-binding pocket on the A variant is located within an eight-stranded β-barrel, similar to that found in the F1*S variant and other lipocalin family proteins. However, the binding region of the A variant is narrower than that of the F1*S variant. In the crystal structures of complexes with DSP and AMT, the two aromatic rings of each drug interact with Phe-49 and Phe-112 at the bottom of the binding pocket. Although the structure of CPZ is similar to those of DSP and AMT, its fused aromatic ring system, which is extended in length by the addition of a chlorine atom, appears to dictate an alternative mode of binding, which explains its nonselective binding to the F1*S and A variant hAGPs. Modeling experiments based on the co-crystal structures suggest that, in complexes of DSP, AMT, or CPZ with the F1*S variant, Phe-114 sterically hinders interactions with DSP and AMT, but not CPZ. © 2011 by The American Society for Biochemistry and Molecular Biology, Inc

Pathogenic variation of Phakopsora pachyrhizi populations in Brazil.

The obligate basidiomycete Phakopsora pachyrhizi is the causal agent of soybean rust that has potential to reduce the yield of soybean drastically. Soybean production in Brazil has been threatened by the rust since the pathogen was first discovered in 2001. To understand pathogenic variation of the rust populations in South America, an evaluation system for soybean rust resistance has been constructed using a set of 16 differential varieties. In this study, the evaluation system was used to investigate pathogenic variation among the P. pachyrhizi populations in Brazil. Samples of P. pachyrhizi were collected from the diseased soybeans in Brazil in the 2007-2008 and 2008-2009 soybean cultivation seasons. In the first season, two rust samples showed similar pattern of the infection types on the differential set, suggesting that the same or similar pathogen population was present in the two locations. The other samples were likely different pathogenic populations. In the second season, different patterns of the infection types were found among the samples. Comparison of the evaluation data from the two seasons demonstrated that pathogenic variation between the seasons was detected in the populations from Rio Grande do Sul and Paraná but was not remarkable in those from Rondônia. This study provides useful knowledge about P. pachyrhizi populations in Brazil to identify the resistant soybean genotypes and target effective cultivars against certain pathogen populations.Edição do Proceedings of the National Soybean Rust Symposium, New Orleans, 2009

1 um Excess Sources in the UKIDSS - I. Three T Dwarfs in the SDSS Southern Equatorial Stripe

We report the discovery of two field brown dwarfs, ULAS J0128-0041 and ULAS J0321+0051, and the rediscovery of ULAS J0226+0051 (IfA 0230-Z1), in the Sloan Digital Sky Survey (SDSS) southern equatorial stripe. They are found in the course of our follow-up observation program of 1 um excess sources in the United Kingdom Infrared Telescope Infrared Deep Sky Survey. The Gemini Multi-Object Spectrographs spectra at red optical wavelengths (6500-10500 A) are presented, which reveal that they are early-T dwarfs. The classification is also supported by their optical to near-infrared colors. It is noted that ULAS J0321+0051 is one of the faintest currently known T dwarfs. The estimated distances to the three objects are 50-110 pc, thus they are among the most distant field T dwarfs known. Dense temporal coverage of the target fields achieved by the SDSS-II Supernova Survey allows us to perform a simple time-series analysis, which leads to the finding of significant proper motions of 150-290 mas/yr or the transverse velocities of 40-100 km/s for ULAS J0128-0041 and ULAS J0226+0051. We also find that there are no detectable, long-term (a-few-year) brightness variations above a few times 0.1 mag for the two brown dwarfs.Comment: Accepted for publication in the Astronomical Journal; Typos correcte

Distribution of Camphor Monooxygenase Genes in Soil Bacteria

In microbial degradation of camphor, the first step is oxidation by multiunit enzyme, camphor monooxygenase, encoded by cam genes (camA,B,C). Seven camphor-utilizing bacterial strains have been isolated from soil at various locations. CamA,B,C genes of Pseudomonas putida strain PpG1 and strain GF2001 were used as probes to explore their abundance in the camphor-utilizing bacteria. Southern analysis revealed that all of the cam genes of GF2001 could hybridize well to the SpeI-digested genomic DNA of strains tested, whereas PpG1 cam genes were not. This result suggested that the GF2001 type cam genes are widely distributed among the camphorutilizing strains in the environment. Thus strain GF2001 and seven newly isolated strains share a common evolutionary origin. Key words: Camphor monooxygenase genes, gene distribution, sail bacteria

A Review of the Properties of Nb3Sn and Their Variation with A15 Composition, Morphology and Strain State

This article gives an overview of the available literature on simplified, well defined (quasi-)homogeneous laboratory samples. After more than 50 years of research on superconductivity in Nb3Sn, a significant amount of results are available, but these are scattered over a multitude of publications. Two reviews exist on the basic properties of A15 materials in general, but no specific review for Nb3Sn is available. This article is intended to provide such an overview. It starts with a basic description of the Niobium-Tin intermetallic. After this it maps the influence of Sn content on the the electron-phonon interaction strength and on the field-temperature phase boundary. The literature on the influence of Cu, Ti and Ta additions will then be briefly summarized. This is followed by a review on the effects of grain size and strain. The article is concluded with a summary of the main results.Comment: Invited Topical Review for Superconductor, Science and Technology. Provisionally scheduled for July 200

On the merit of a Central Limit Theorem-based approximation in statistical physics

The applicability conditions of a recently reported Central Limit Theorem-based approximation method in statistical physics are investigated and rigorously determined. The failure of this method at low and intermediate temperature is proved as well as its inadequacy to disclose quantum criticalities at fixed temperatures. Its high temperature predictions are in addition shown to coincide with those stemming from straightforward appropriate expansions up to (k_B T)^(-2). Our results are clearly illustrated by comparing the exact and approximate temperature dependence of the free energy of some exemplary physical systems.Comment: 12 pages, 1 figur

1 um Excess Sources in the UKIDSS - I. Three T Dwarfs in the SDSS Southern Equatorial Stripe

We report the discovery of two field brown dwarfs, ULAS J0128-0041 and ULAS J0321+0051, and the rediscovery of ULAS J0226+0051 (IfA 0230-Z1), in the Sloan Digital Sky Survey (SDSS) southern equatorial stripe. They are found in the course of our follow-up observation program of 1 um excess sources in the United Kingdom Infrared Telescope Infrared Deep Sky Survey. The Gemini Multi-Object Spectrographs spectra at red optical wavelengths (6500-10500 A) are presented, which reveal that they are early-T dwarfs. The classification is also supported by their optical to near-infrared colors. It is noted that ULAS J0321+0051 is one of the faintest currently known T dwarfs. The estimated distances to the three objects are 50-110 pc, thus they are among the most distant field T dwarfs known. Dense temporal coverage of the target fields achieved by the SDSS-II Supernova Survey allows us to perform a simple time-series analysis, which leads to the finding of significant proper motions of 150-290 mas/yr or the transverse velocities of 40-100 km/s for ULAS J0128-0041 and ULAS J0226+0051. We also find that there are no detectable, long-term (a-few-year) brightness variations above a few times 0.1 mag for the two brown dwarfs.Comment: Accepted for publication in the Astronomical Journal; Typos correcte

Carbon nanotubes as electrically active nanoreactors for multi-step inorganic synthesis: sequential transformations of molecules to nanoclusters, and nanoclusters to nanoribbons

In organic synthesis, the composition and structure of products are predetermined by the reaction conditions; however, the synthesis of well-defined inorganic nanostructures often presents a significant challenge yielding non-stoichiometric or polymorphic products. In this study, confinement in the nanoscale cavities of single-walled carbon nanotubes (SWNT) provides a new approach for multi-step inorganic synthesis where sequential chemical transformations take place within the same nanotube. In the first step, SWNT donate electrons to the reactant iodine molecules (I2) transforming them to iodide anions (I-). These then react with metal hexacarbonyls (M(CO)6, M = Mo or W) in the next step yielding anionic nanoclusters [M6I14]2-, the size and composition of which are strictly dictated by the nanotube cavity, as demonstrated by aberration corrected high resolution transmission electron microscopy (AC-HRTEM), scanning transmission electron microscopy (STEM) and energy dispersive X-ray (EDX) spectroscopy. Atoms in the nanoclusters [M6I14]2- are arranged in a perfect octahedral geometry and can engage in further chemical reactions within the nanotube, either reacting with each other leading to a new polymeric phase of molybdenum iodide [Mo6I12]n, or with hydrogen sulphide gas giving rise to nanoribbons of molybdenum/tungsten disulphide [MS2]n in the third step of the synthesis. Electron microscopy measurements demonstrate that the products of the multi-step inorganic transformations are precisely controlled by the SWNT nanoreactor, with complementary Raman spectroscopy revealing the remarkable property of SWNT to act as a reservoir of electrons during the chemical transformation. The electron transfer from the host-nanotube to the reacting guest-molecules is essential for stabilising the anionic metal iodide 2 nanoclusters and for their further transformation to metal disulphide nanoribbons synthesised in the nanotubes in high yield

Type-Based Deadlock-Freedom Verification for Non-Block-Structured Lock Primitives and Mutable References

Abstract. We present a type-based deadlock-freedom verification for concurrent programs with non-block-structured lock primitives and mu-table references. Though those two features are frequently used, they are not dealt with in a sufficient manner by previous verification methods. Our type system uses a novel combination of lock levels, obligations and ownerships. Lock levels are used to guarantee that locks are acquired in a specific order. Obligations and ownerships guarantee that an acquired lock is released exactly once.