7,030 research outputs found

    Numerical Strategies of Computing the Luminosity Distance

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    We propose two efficient numerical methods of evaluating the luminosity distance in the spatially flat {\Lambda}CDM universe. The first method is based on the Carlson symmetric form of elliptic integrals, which is highly accurate and can replace numerical quadratures. The second method, using a modified version of Hermite interpolation, is less accurate but involves only basic numerical operations and can be easily implemented. We compare our methods with other numerical approximation schemes and explore their respective features and limitations. Possible extensions of these methods to other cosmological models are also discussed.Comment: 4 pages, 2 figures. v2: A minor error in the last equation has been corrected (conclusions are not affected). v3: Accepted by MNRA

    Structure and substrate selectivity of the 750-kDa α6β6 holoenzyme of geranyl-CoA carboxylase.

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    Geranyl-CoA carboxylase (GCC) is essential for the growth of Pseudomonas organisms with geranic acid as the sole carbon source. GCC has the same domain organization and shares strong sequence conservation with the related biotin-dependent carboxylases 3-methylcrotonyl-CoA carboxylase (MCC) and propionyl-CoA carboxylase (PCC). Here we report the crystal structure of the 750-kDa α6β6 holoenzyme of GCC, which is similar to MCC but strikingly different from PCC. The structures provide evidence in support of two distinct lineages of biotin-dependent acyl-CoA carboxylases, one carboxylating the α carbon of a saturated organic acid and the other carboxylating the γ carbon of an α-β unsaturated acid. Structural differences in the active site region of GCC and MCC explain their distinct substrate preferences. Especially, a glycine residue in GCC is replaced by phenylalanine in MCC, which blocks access by the larger geranyl-CoA substrate. Mutation of this residue in the two enzymes can change their substrate preferences

    PUMA amplifies necroptosis signaling by activating cytosolic DNA sensors.

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    Necroptosis, a form of regulated necrotic cell death, is governed by RIP1/RIP3-mediated activation of MLKL. However, the signaling process leading to necroptotic death remains to be elucidated. In this study, we found that PUMA, a proapoptotic BH3-only Bcl-2 family member, is transcriptionally activated in an RIP3/MLKL-dependent manner following induction of necroptosis. The induction of PUMA, which is mediated by autocrine TNF-α and enhanced NF-κB activity, contributes to necroptotic death in RIP3-expressing cells with caspases inhibited. On induction, PUMA promotes the cytosolic release of mitochondrial DNA and activation of the DNA sensors DAI/Zbp1 and STING, leading to enhanced RIP3 and MLKL phosphorylation in a positive feedback loop. Furthermore, deletion of PUMA partially rescues necroptosis-mediated developmental defects in FADD-deficient embryos. Collectively, our results reveal a signal amplification mechanism mediated by PUMA and cytosolic DNA sensors that is involved in TNF-driven necroptotic death in vitro and in vivo

    Changes in the milk metabolome of the Giant Panda (Ailuropoda melanoleuca) with time after birth: three phases in early lactation and progressive individual differences

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    Ursids (bears) in general, and giant pandas in particular, are highly altricial at birth. The components of bear milks and their changes with time may be uniquely adapted to nourish relatively immature neonates, protect them from pathogens, and support the maturation of neonatal digestive physiology. Serial milk samples collected from three giant pandas in early lactation were subjected to untargeted metabolite profiling and multivariate analysis. Changes in milk metabolites with time after birth were analysed by Principal Component Analysis, Hierarchical Cluster Analysis and further supported by Orthogonal Partial Least Square-Discriminant Analysis, revealing three phases of milk maturation: days 1–6 (Phase 1), days 7–20 (Phase 2), and beyond day 20 (Phase 3). While the compositions of Phase 1 milks were essentially indistinguishable among individuals, divergences emerged during the second week of lactation. OPLS regression analysis positioned against the growth rate of one cub tentatively inferred a correlation with changes in the abundance of a trisaccharide, isoglobotriose, previously observed to be a major oligosaccharide in ursid milks. Three artificial milk formulae used to feed giant panda cubs were also analysed, and were found to differ markedly in component content from natural panda milk. These findings have implications for the dependence of the ontogeny of all species of bears, and potentially other members of the Carnivora and beyond, on the complexity and sequential changes in maternal provision of micrometabolites in the immediate period after birth

    Strong terahertz radiation from a liquid-water line

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    Terahertz radiation generation from liquid water has long been considered impossible due to strong absorption. A few very recent works reported terahertz generation from water, but the mechanism is not clear and the efficiency demands to be enhanced. We show experimentally that strong single-cycle terahertz radiation with field strength of 0.2MVcm-1 is generated from a water line (or column) of approximately 200μm in diameter irradiated by a mJ femtosecond laser beam. This strength is 100-fold higher than that produced from air using single-color pumping. We attribute the mechanism to the laser-ponderomotive-force-induced current with the symmetry broken around the water-column interface. This mechanism can explain our following observations: the radiation can be generated only when the laser propagation axis deviates from the column center; the deviation determines its field strength and polarity; it is always p polarized no matter whether the laser is p or s polarized. This study provides a simple and efficient scheme of table-top terahertz sources based on liquid water

    Prolonged transition time between colostrum and mature milk in a bear, the giant panda, Ailuropoda melanoleuca

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    Bears produce the most altricial neonates of any placental mammal. We hypothesized that the transition from colostrum to mature milk in bears reflects a temporal and biochemical adaptation for altricial development and immune protection. Comparison of bear milks with milks of other eutherians yielded distinctive protein profiles. Proteomic and metabolomic analysis of serial milk samples collected from six giant pandas showed a prolonged transition from colostrum to main-phase lactation over approximately 30 days. Particularly striking are the persistence or sequential appearance of adaptive and innate immune factors. The endurance of immunoglobulin G suggests an unusual duration of trans-intestinal absorption of maternal antibodies, and is potentially relevant to the underdeveloped lymphoid system of giant panda neonates. Levels of certain milk oligosaccharides known to exert anti-microbial activities and/or that are conducive to the development of neonatal gut microbiomes underwent an almost complete changeover around days 20–30 postpartum, coincident with the maturation of the protein profile. A potential metabolic marker of starvation was detected, the prominence of which may reflect the natural postpartum period of anorexia in giant panda mothers. Early lactation in giant pandas, and possibly in other ursids, appears to be adapted for the unique requirements of unusually altricial eutherian neonates

    Metabolomic profiling and stable isotope labelling of Trichomonas vaginalis and Tritrichomonas foetus reveal major differences in amino acid metabolism including the production of 2-hydroxyisocaproic acid, cystathionine and S-methylcysteine

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    Trichomonas vaginalis and Tritrichomonas foetus are pathogens that parasitise, respectively, human and bovine urogenital tracts causing disease. Using LC-MS, reference metabolomic profiles were obtained for both species and stable isotope labelling with D-[U-13C6] glucose was used to analyse central carbon metabolism. This facilitated a comparison of the metabolic pathways of T. vaginalis and T. foetus, extending earlier targeted biochemical studies. 43 metabolites, whose identities were confirmed by comparison of their retention times with authentic standards, occurred at more than 3-fold difference in peak intensity between T. vaginalis and T. foetus. 18 metabolites that were removed from or released into the medium during growth also showed more than 3-fold difference between the species. Major differences were observed in cysteine and methionine metabolism in which homocysteine, produced as a bi-product of trans-methylation, is catabolised by methionine γ-lyase in T. vaginalis but converted to cystathionine in T. foetus. Both species synthesise methylthioadenosine by an unusual mechanism, but it is not used as a substrate for methionine recycling. T. vaginalis also produces and exports high levels of S-methylcysteine, whereas only negligible levels were found in T. foetus which maintains significantly higher intracellular levels of cysteine. 13C-labeling confirmed that both cysteine and S-methylcysteine are synthesised by T. vaginalis; S-methylcysteine can be generated by recombinant T. vaginalis cysteine synthase using phosphoserine and methanethiol. T. foetus contained higher levels of ornithine and citrulline than T. vaginalis and exported increased levels of putrescine, suggesting greater flux through the arginine dihydrolase pathway. T. vaginalis produced and exported hydroxy acid derivatives of certain amino acids, particularly 2-hydroxyisocaproic acid derived from leucine, whereas negligible levels of these metabolites occurred in T. foetus
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