Growth- and substrate-dependent transcription of formate dehydrogenase and hydrogenase coding genes in Syntrophobacter fumaroxidans and Methanospirillum hungatei

Transcription of genes coding for formate dehydrogenases (fdh genes) and hydrogenases (hyd genes) in Syntrophobacter fumaroxidans and Methanospirillum hungatei was studied following growth under different conditions. Under all conditions tested, all fdh and hyd genes were transcribed. However, transcription levels of the individual genes varied depending on the substrate and growth conditions. Our results strongly suggest that in syntrophically grown S. fumaroxidans cells, the [FeFe]-hydrogenase (encoded by Sfum_844-46), FDH1 (Sfum_2703-06) and Hox (Sfum_2713-16) may confurcate electrons from NADH and ferredoxin to protons and carbon dioxide to produce hydrogen and formate, respectively. Based on bioinformatic analysis, a membrane-integrated energy-converting [NiFe]-hydrogenase (Mhun_1741-46) of M. hungatei might be involved in the energy-dependent reduction of CO2 to formylmethanofuran. The best candidates for F420-dependent N5,N10-methyl-H4 MPT and N5,N10,-methylene-H4MPT reduction are the cytoplasmic [NiFe]-hydrogenase and FDH1. 16S rRNA ratios indicate that in one of the triplicate co-cultures of S. fumaroxidans and M. hungatei, less energy was available for S. fumaroxidans. This led to enhanced transcription of genes coding for the Rnf-complex (Sfum_2694-99) and of several fdh and hyd genes. The Rnf-complex probably reoxidized NADH with ferredoxin reduction, followed by ferredoxin oxidation by the induced formate dehydrogenases and hydrogenase

Exploring the Added Value of Population Distribution Indicators for Studies of European Urban Form

In Europe, landscape metrics dominate studies that apply quantitative analyses to urban form. Indicators describing population distribution in more detail than just population density, which in Europe are often neglected because of the difficulty in data acquisition, are likely to be more adequate for describing the socioeconomic perspective on urban form. This study aims to disclose the linkage between landscape metrics and population distribution metrics and to provide a better understanding of population distribution patterns. In our study, we quantified urban form in 35 European cities using the most common indicators from both groups of indicators, including measures for the gradient of population density with distance from the city center or (in-) equality of population distribution. We found that landscape metrics correlate only weakly with population distribution indicators by analyzing the correlation matrix. To obtain more insight into the largely neglected group of population distribution indicators, we also applied a regression analysis to understand their underlying information. The results show that population distribution indicators are related to other basic characteristics of cities, such as planning coordination and latitude. The indicated influence of national planning regime on urban form could stimulate further discussion on the effectiveness of urban planning measures. Our study demonstrates that population distribution indicators provide a different perspective than landscape metrics in describing urban form. We therefore stress that it is essential to include population distribution indicators also for describing European cities when aiming to comprehensively describe urban form

ECC2K-130 on NVIDIA GPUs

A major cryptanalytic computation is currently underway on multiple platforms, including standard CPUs, FPGAs, PlayStations and Graphics Processing Units (GPUs), to break the Certicom ECC2K-130 challenge. This challenge is to compute an elliptic-curve discrete logarithm on a Koblitz curve over $\rm F_{2^{131}}$ . Optimizations have reduced the cost of the computation to approximately 277 bit operations in 261 iterations. GPUs are not designed for fast binary-field arithmetic; they are designed for highly vectorizable floating-point computations that fit into very small amounts of static RAM. This paper explains how to optimize the ECC2K-130 computation for this unusual platform. The resulting GPU software performs more than 63 million iterations per second, including 320 million $\rm F_{2^{131}}$ multiplications per second, on a $500 NVIDIA GTX 295 graphics card. The same techniques for finite-field arithmetic and elliptic-curve arithmetic can be reused in implementations of larger systems that are secure against similar attacks, making GPUs an interesting option as coprocessors when a busy Internet server has many elliptic-curve operations to perform in parallel

Near-Earth asteroid sample return missions

The rate of discovery of new NEAs and the success of D-S 1 and NEAR-Shoemaker, suggest that sample return from NEAs is now technically feasible. Here we present a summary of a recent workshop on the topic

The spectrum of D_s mesons from lattice QCD

The spectrum of orbitally excited $D_s$ mesons is computed in the continuum limit of quenched lattice QCD. The results are consistent with the interpretation that the narrow resonance in the $D_s \pi^0$ channel discovered by the BABAR Collaboration is a $J^P=0^+$ $c\bar{s}$ meson. Furthermore, within statistical errors, the $1^+-1^-$ and the $0^+-0^-$ mass splittings are equal, in agreement with the chiral multiplet structure predicted by heavy hadron chiral effective theory. On our coarsest lattice we present results from the first study of orbitally excited $D_s$ mesons with two flavors of dynamical quarks, with mass slightly larger than the strange quark mass. These results are consistent with the quenched data.Comment: 8 pages, 2 figure

Interaction of N solitons in the massive Thirring model and optical gap system: the Complex Toda Chain Model

Using the Karpman-Solov''ev quasiparticle approach for soliton-soliton interaction I show that the train propagation of N well separated solitons of the massive Thirring model is described by the complex Toda chain with N nodes. For the optical gap system a generalised (non-integrable) complex Toda chain is derived for description of the train propagation of well separated gap solitons. These results are in favor of the recently proposed conjecture of universality of the complex Toda chain.Comment: RevTex, 23 pages, no figures. Submitted to Physical Review

Taurocholate-stimulated leukotriene C4 biosynthesis and leukotriene C4-stimulated choleresis in isolated rat liver

BACKGROUND/AIMS: Cysteinyl-containing leukotrienes seem to exert a cholestatic effect. However, leukotriene inhibitors were found to reduce bile salt efflux in isolated rat hepatocytes, suggesting a role for leukotrienes in bile flow formation. METHODS: In the isolated rat liver, the effects of two different concentrations of leukotriene C4 on bile flow and bile salt excretion are analyzed, as well as the possible effect of taurocholate on the hepatic production of cysteinyl-containing leukotrienes. RESULTS: Leukotriene C4 (0.25 fmol) increased bile salt excretion (+22.2%; P < 0.05), whereas a much higher dose (0.25 x 10(6) fmol) showed the known cholestatic effect, reducing bile salt excretion (-25.9%; P < 0.01). These dose-dependent biphasic effects were specific because they could be prevented by the simultaneous administration of cysteinyl-containing leukotriene antagonists. On the other hand, taurocholate administration induced a dose-dependent increase in biliary excretion of cysteinyl-containing leukotrienes. Furthermore, taurocholate increased messenger RNA levels of 5-lipoxygenase, a key enzyme in leukotriene biosynthesis. Taurocholate increase of hepatocyte intracellular calcium was not significant, suggesting that taurocholate effects are not mediated by stimulation of calcium metabolism. CONCLUSIONS: These results constitute evidence for the existence of a positive feedback mechanism by which bile salts stimulate the synthesis of leukotrienes that, in turn, stimulate bile salt excretion

Genome-wide association study of disease resilience traits from a natural polymicrobial disease challenge model in pigs identifies the importance of the major histocompatibility complex region

Infectious diseases cause tremendous financial losses in the pork industry, emphasizing the importance of disease resilience, which is the ability of an animal to maintain performance under disease. Previously, a natural polymicrobial disease challenge model was established, in which pigs were challenged in the late nursery phase by multiple pathogens to maximize expression of genetic differences in disease resilience. Genetic analysis found that performance traits in this model, including growth rate, feed and water intake, and carcass traits, as well as clinical disease phenotypes, were heritable and could be selected for to increase disease resilience of pigs. The objectives of the current study were to identify genomic regions that are associated with disease resilience in this model, using genome-wide association studies and fine-mapping methods, and to use gene set enrichment analyses to determine whether genomic regions associated with disease resilience are enriched for previously published quantitative trait loci, functional pathways, and differentially expressed genes subject to physiological states. Multiple quantitative trait loci were detected for all recorded performance and clinical disease traits. The major histocompatibility complex region was found to explain substantial genetic variance for multiple traits, including for growth rate in the late nursery (12.8%) and finisher (2.7%), for several clinical disease traits (up to 2.7%), and for several feeding and drinking traits (up to 4%). Further fine mapping identified 4 quantitative trait loci in the major histocompatibility complex region for growth rate in the late nursery that spanned the subregions for class I, II, and III, with 1 single-nucleotide polymorphism in the major histocompatibility complex class I subregion capturing the largest effects, explaining 0.8–27.1% of genetic variance for growth rate and for multiple clinical disease traits. This singlenucleotide polymorphism was located in the enhancer of TRIM39 gene, which is involved in innate immune response. The major histocompatibility complex region was pleiotropic for growth rate in the late nursery and finisher, and for treatment and mortality rates. Growth rate in the late nursery showed strong negative genetic correlations in the major histocompatibility complex region with treatment or mortality rates (–0.62 to –0.85) and a strong positive genetic correlation with growth rate in the finisher (0.79). Gene set enrichment analyses found genomic regions associated with resilience phenotypes to be enriched for previously identified disease susceptibility and immune capacity quantitative trait loci, for genes that were differentially expressed following bacterial or virus infection and immune response, and for gene ontology terms related to immune and inflammatory response. In conclusion, the major histocompatibility complex and other quantitative trait loci that harbor immune-related genes were identified to be associated with disease resilience traits in a large-scale natural polymicrobial disease challenge. The major histocompatibility complex region was pleiotropic for growth rate under challenge and for clinical disease traits. Four quantitative trait loci were identified across the class I, II, and III subregions of the major histocompatibility complex for nursery growth rate under challenge, with 1 single-nucleotide polymorphism in the major histocompatibility complex class I subregion capturing the largest effects. The major histocompatibility complex and other quantitative trait loci identified play an important role in host response to infectious diseases and can be incorporated in selection to improve disease resilience, in particular the identified singlenucleotide polymorphism in the major histocompatibility complex class I subregion

Mutational Analysis of Hedgehog Signaling Pathway Genes in Human Malignant Mesothelioma

Background The Hedgehog (HH) signaling pathway is critical for embryonic development and adult homeostasis. Recent studies have identified regulatory roles for this pathway in certain cancers with mutations in the HH pathway genes. The extent to which mutations of the HH pathway genes are involved in the pathogenesis of malignant mesothelioma (MMe) is unknown. Methodology/Principal Findings Real-time PCR analysis of HH pathway genes PTCH1, GLI1 and GLI2 were performed on 7 human MMe cell lines. Exon sequencing of 13 HH pathway genes was also performed in cell lines and human MMe tumors. In silico programs were used to predict the likelihood that an amino-acid substitution would have a functional effect. GLI1, GLI2 and PTCH1 were highly expressed in MMe cells, indicative of active HH signaling. PTCH1, SMO and SUFU mutations were found in 2 of 11 MMe cell lines examined. A non-synonymous missense SUFU mutation (p.T411M) was identified in LO68 cells. In silico characterization of the SUFU mutant suggested that the p.T411M mutation might alter protein function. However, we were unable to demonstrate any functional effect of this mutation on Gli activity. Deletion of exons of the PTCH1 gene was found in JU77 cells, resulting in loss of one of two extracellular loops implicated in HH ligand binding and the intracellular C-terminal domain. A 3-bp insertion (69_70insCTG) in SMO, predicting an additional leucine residue in the signal peptide segment of SMO protein was also identified in LO68 cells and a MMe tumour. Conclusions/Significance We identified the first novel mutations in PTCH1, SUFU and SMO associated with MMe. Although HH pathway mutations are relatively rare in MMe, these data suggest a possible role for dysfunctional HH pathway in the pathogenesis of a subgroup of MMe and help rationalize the exploration of HH pathway inhibitors for MMe therapy

Supermassive Binaries and Extragalactic Jets

Some quasars show Doppler shifted broad emission line peaks. I give new statistics of the occurrence of these peaks and show that, while the most spectacular cases are in quasars with strong radio jets inclined to the line of sight, they are also almost as common in radio-quiet quasars. Theories of the origin of the peaks are reviewed and it is argued that the displaced peaks are most likely produced by the supermassive binary model. The separations of the peaks in the 3C 390.3-type objects are consistent with orientation-dependent "unified models" of quasar activity. If the supermassive binary model is correct, all members of "the jet set" (astrophysical objects showing jets) could be binaries.Comment: 31 pages, PostScript, missing figure is in ApJ 464, L105 (see http://www.aas.org/ApJ/v464n2/5736/5736.html