Use of Shotgun Metagenomics and Metabolomics to Evaluate the Impact of Glyphosate or Roundup MON 52276 on the Gut Microbiota and Serum Metabolome of Sprague-Dawley Rats

Background: There is intense debate on whether glyphosate can inhibit the shikimate pathway of gastrointestinal microorganisms, with potential health implications. Objectives: We tested whether glyphosate or its representative EU herbicide formulation Roundup MON 52276 affects the rat gut microbiome. Methods: We combined cecal microbiome shotgun metagenomics with serum and cecum metabolomics to assess the effects of glyphosate [0.5, 50, 175 mg/kg body weight (BW) per day] or MON 52276 at the same glyphosate-equivalent doses, in a 90-d toxicity test in rats. Results: Glyphosate and MON 52276 treatment resulted in ceca accumulation of shikimic acid and 3-dehydroshikimic acid, suggesting inhibition of 5-enolpyruvylshikimate-3-phosphate synthase of the shikimate pathway in the gut microbiome. Cysteinylglycine, γ-glutamylglutamine, and valylglycine levels were elevated in the cecal microbiome following glyphosate and MON 52276 treatments. Altered cecum metabolites were not differentially expressed in serum, suggesting that the glyphosate and MON 52276 impact on gut microbial metabolism had limited consequences on physiological biochemistry. Serum metabolites differentially expressed with glyphosate treatment were associated with nicotinamide, branched-chain amino acid, methionine, cysteine, and taurine metabolism, indicative of a response to oxidative stress. MON 52276 had similar, but more pronounced, effects than glyphosate on the serum metabolome. Shotgun metagenomics of the cecum showed that treatment with glyphosate and MON 52276 resulted in higher levels of Eggerthella spp., Shinella zoogleoides, Acinetobacter johnsonii, and Akkermansia muciniphila. Shinella zoogleoides was higher only with MON 52276 exposure. In vitro culture assays with Lacticaseibacillus rhamnosus strains showed that Roundup GT plus inhibited growth at concentrations at which MON 52276 and glyphosate had no effect. Discussion: Our study highlights the power of multi-omics approaches to investigate the toxic effects of pesticides. Multi-omics revealed that glyphosate and MON 52276 inhibited the shikimate pathway in the rat gut microbiome. Our findings could be used to develop biomarkers for epidemiological studies aimed at evaluating the effects of glyphosate herbicides on humans

Progress in Monte Carlo calculations of Fermi systems: normal liquid 3He

The application of the diffusion Monte Carlo method to a strongly interacting Fermi system as normal liquid $^3$He is explored. We show that the fixed-node method together with the released-node technique and a systematic method to analytically improve the nodal surface constitute an efficient strategy to improve the calculation up to a desired accuracy. This methodology shows unambiguously that backflow correlations, when properly optimized, are enough to generate an equation of state of liquid $^3$He in excellent agreement with experimental data from equilibrium up to freezing.Comment: 14 pages, 3 eps figure

Momentum distributions in ^3He-^4He liquid mixtures

We present variational calculations of the one-body density matrices and momentum distributions for ^3He-^4He mixtures in the zero temperature limit, in the framework of the correlated basis functions theory. The ground-state wave function contains two- and three-body correlations and the matrix elements are computed by (Fermi)Hypernetted Chain techniques. The dependence on the ^3He concentration (x_3) of the ^4He condensate fraction $(n_0^{(4)})$ and of the ^3He pole strength (Z_F) is studied along the P=0 isobar. At low ^3He concentration, the computed ^4He condensate fraction is not significantly affected by the ^3He statistics. Despite of the low x_3 values, Z_F is found to be quite smaller than that of the corresponding pure ^3He because of the strong ^3He-^4He correlations and of the overall, large total density \rho. A small increase of $n_0^{(4)}$ along x_3 is found, which is mainly due to the decrease of \rho respect to the pure ^4He phase.Comment: 23 pages, 7 postscript figures, Revte

Formas de uréia e doses de nitrogênio em cobertura na qualidade fisiológica de sementes de trigo.

A adubação nitrogenada, além de aumentar a produtividade, pode favorecer a qualidade fisiológica das sementes. O trigo no Paraná é geralmente cultivado após a cultura da soja, com isso a palha da soja e outros fatores do solo podem minimizar o efeito do nitrogênio no trigo. O objetivo do trabalho foi avaliar o efeito de doses de adubação nitrogenada em cobertura e de diferentes formas de ureia, na qualidade fisiológica de sementes de genótipos de trigo. Os experimentos foram conduzidos em Londrina e Ponta Grossa-PR. As áreas experimentais são manejadas no sistema de plantio direto com rotação de culturas, sendo a soja a cultura anterior. Foram avaliadas sementes de três genótipos de trigo (BRS 208, BRS Pardela e IWT 04008) cultivados sob quatro doses de nitrogênio em cobertura (0, 40, 80 e 120 kg ha-1), provenientes de três formas de ureia (convencional, com inibidor de urease e protegida). A adubação nitrogenada de cobertura foi realizada durante o estádio de perfilhamento, aos 20 dias após a emergência. Avaliou-se o teor de nitrogênio nas sementes, a massa de 1000 sementes, a germinação e o vigor (primeira contagem, frio, emergência, massa seca de plântulas, envelhecimento acelerado e condutividade elétrica). Os genótipos de trigo foram analisados conjuntamente para cada local. A linhagem IWT 04008 e a cultivar BRS Pardela apresentam sementes com qualidade fisiológica superior a cultivar BRS 208. Somente em Londrina, em consequência do acamamento, as doses de nitrogênio influenciaram negativamente a massa de 1000 grãos e a condutividade elétrica e, positivamente o teor de proteína. As formas de ureia e as doses de nitrogênio não alteram a qualidade fisiológica das sementes de diferentes genótipos de trigo

The Path Integral Monte Carlo Calculation of Electronic Forces

We describe a method to evaluate electronic forces by Path Integral Monte Carlo (PIMC). Electronic correlations, as well as thermal effects, are included naturally in this method. For fermions, a restricted approach is used to avoid the ``sign'' problem. The PIMC force estimator is local and has a finite variance. We applied this method to determine the bond length of H$_2$ and the chemical reaction barrier of H+H$_2\longrightarrow$H$_2$+H. At low temperature, good agreement is obtained with ground state calculations. We studied the proton-proton interaction in an electron gas as a simple model for hydrogen impurities in metals. We calculated the force between the two protons at two electronic densities corresponding to Na ($r_s=3.93$) and Al ($r_s=2.07$) using a supercell with 38 electrons. The result is compared to previous calculations. We also studied the effect of temperature on the proton-proton interaction. At very high temperature, our result agrees with the Debye screening of electrons. As temperature decreases, the Debye theory fails both because of the strong degeneracy of electrons and most importantly, the formation of electronic bound states around the protons.Comment: 18 pages, 10 figure

A Constrained Path Monte Carlo Method for Fermion Ground States

We describe and discuss a recently proposed quantum Monte Carlo algorithm to compute the ground-state properties of various systems of interacting fermions. In this method, the ground state is projected from an initial wave function by a branching random walk in an over-complete basis of Slater determinants. By constraining the determinants according to a trial wave function $|\psi_T\rangle$, we remove the exponential decay of signal-to-noise ratio characteristic of the sign problem. The method is variational and is exact if $|\psi_T\rangle$ is exact. We illustrate the method by describing in detail its implementation for the two-dimensional one-band Hubbard model. We show results for lattice sizes up to $16\times 16$ and for various electron fillings and interaction strengths. Besides highly accurate estimates of the ground-state energy, we find that the method also yields reliable estimates of other ground-state observables, such as superconducting pairing correlation functions. We conclude by discussing possible extensions of the algorithm.Comment: 29 pages, RevTex, 3 figures included; submitted to Phys. Rev.

Multi-omics phenotyping of the gut-liver axis reveals metabolic perturbations from a low-dose pesticide mixture in rats.

Health effects of pesticides are not always accurately detected using the current battery of regulatory toxicity tests. We compared standard histopathology and serum biochemistry measures and multi-omics analyses in a subchronic toxicity test of a mixture of six pesticides frequently detected in foodstuffs (azoxystrobin, boscalid, chlorpyrifos, glyphosate, imidacloprid and thiabendazole) in Sprague-Dawley rats. Analysis of water and feed consumption, body weight, histopathology and serum biochemistry showed little effect. Contrastingly, serum and caecum metabolomics revealed that nicotinamide and tryptophan metabolism were affected, which suggested activation of an oxidative stress response. This was not reflected by gut microbial community composition changes evaluated by shotgun metagenomics. Transcriptomics of the liver showed that 257 genes had their expression changed. Gene functions affected included the regulation of response to steroid hormones and the activation of stress response pathways. Genome-wide DNA methylation analysis of the same liver samples showed that 4,255 CpG sites were differentially methylated. Overall, we demonstrated that in-depth molecular profiling in laboratory animals exposed to low concentrations of pesticides allows the detection of metabolic perturbations that would remain undetected by standard regulatory biochemical measures and which could thus improve the predictability of health risks from exposure to chemical pollutants

High-momentum dynamic structure function of liquid 3He-4He mixtures: a microscopic approach

The high-momentum dynamic structure function of liquid 3He-4He mixtures has been studied introducing final state effects. Corrections to the impulse approximation have been included using a generalized Gersch-Rodriguez theory that properly takes into account the Fermi statistics of 3He atoms. The microscopic inputs, as the momentum distributions and the two-body density matrices, correspond to a variational (fermi)-hypernetted chain calculation. The agreement with experimental data obtained at $q=23.1$ \AA$^{-1}$ is not completely satisfactory, the comparison being difficult due to inconsistencies present in the scattering measurements. The significant differences between the experimental determinations of the 4He condensate fraction and the 3He kinetic energy, and the theoretical results, still remain unsolved.Comment: 18 pages, 11 figures, to appear in Phys. Rev.

The Coupled Electron-Ion Monte Carlo Method

In these Lecture Notes we review the principles of the Coupled Electron-Ion Monte Carlo methods and discuss some recent results on metallic hydrogen.Comment: 38 pages, 6 figures, Lecture notes for the International School of Solid State Physics, 34th course: "Computer Simulation in Condensed Matter: from Materials to Chemical Biology", 20 July-1 August 2005 Erice (Italy). To appear in Lecture Notes in Physics (2006

Momentum distribution of liquid helium

We have obtained the one--body density matrix and the momentum distribution $n(p)$ of liquid $^4$He at $T=3D0^o$K from Diffusion Monte Carlo (DMC) simulations, using trial functions optimized via the Euler Monte Carlo (EMC) method. We find a condensate fraction smaller than in previous calculations. Though we do not explicitly include long--range correlations in our calculations, we get a momentum distribution at long wavelength which is compatible with the presence of long--range correlations in the exact wave function. We have also studied $^3$He, using fixed--node DMC, with nodes and trial functions provided by the EMC. In particular, we analyze the momentum distribution $n(p)$ with respect to the discontinuity $Z$ as well as the singular behavior, at the Fermi surface. We also show that an approximate factorization of the one-body density matrix $\rho(r)\simeq \rho_0(r)\rho_B(r)$ holds, with $\rho_0(r)$ and $\rho_B(r)$ respectively the density matrix of the ideal Fermi gas and the density matrix of a Bose $^3$He.Comment: 10 pages, REVTeX, 12 figure