Lipase-Catalyzed Acetylation and Esterification of Bile Acids

In this chapter we describe the application of lipases as catalysts in reactions on a relevant family of steroids: the bile acids. Twenty three mono-, diacetyl and ester derivatives of deoxycholic-, chenodeoxycholic-, lithocholic- and cholic acid, fifteen of them new compounds, were obtained through lipase-catalyzed acetylation, esterification and alcoholysis reactions in very good to excellent yield and a highly regioselective way. Among them, acetylated ester products, in which the lipase catalyzed both reactions in one-pot, were obtained. The influence of various reaction parameters in the enzymatic reactions, such as enzyme source, nucleophile/substrate ratio, enzyme/substrate ratio, solvent and temperature, was studied. Some of the reported products are novel and it is not possible to obtain them satisfactorily by following traditional synthetic procedures. Due to its singular structure containing three hydroxyl groups, cholic acid showed a different behavior in the enzymatic reactions, from that observed for the other three bile acids studied. In order to shed light to different behavior of bile acids in the enzymatic reactions, molecular modeling was applied to substrates and some derivatives.Fil: Baldessari, Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; ArgentinaFil: Garcia Liñares, Guadalupe Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; Argentin

Chemoenzymatic Synthesis of Nitrogen Polymers with Biomedical Applications Catalyzed by Lipases

The application of Candida antarctica lipase B as catalyst in the synthesis of two examples of nitrogen polymers is described. Firstly, we report anovel linear polyamidoamine oligomer, obtained by polymerization of ethyl acrylate and N-methyl-1,3-diaminopropane, catalyzed by Candida antarctica lipase B immobilized on polypropylene. The second part of the chapter describes an efficient route for the synthesis of a novel β-peptoid oligomer with hydroxyalkyl pendant groups in the nitrogen atom, through the polymerization of ethyl N-(2-hydroxyethyl)-β-alaninate catalyzed by Candida antarctica lipase B physically adsorbed within a macroporous poly(methyl methacrylate-co-butyl methacrylate) resin.Moreover,two derivatives of the β-peptoid oligomer were prepared: by acetylation and by grafting polycaprolactone. This last process was performed through ring opening polymerization of caprolactone from the β-peptoid pendant hydroxyl groups and afforded a brush copolymer. The products were blended with polycaprolactone to make films by solvent casting. The inclusion of the acyl derivatives of the β-peptoid to polycaprolactone affected the morphology of the film yielding micro- and nanostructured patterns.The obtained products showed biomedical applications.Fil: Baldessari, Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; ArgentinaFil: Garcia Liñares, Guadalupe Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; Argentin

Functional crosstalk of PGC-1 coactivators and inflammation in skeletal muscle pathophysiology

Skeletal muscle is an organ involved in whole body movement and energy metabolism with the ability to dynamically adapt to different states of (dis-)use. At a molecular level, the peroxisome proliferator-activated receptor γ coactivators 1 (PGC-1s) are important mediators of oxidative metabolism in skeletal muscle and in other organs. Musculoskeletal disorders as well as obesity and its sequelae are associated with PGC-1 dysregulation in muscle with a concomitant local or systemic inflammatory reaction. In this review, we outline the function of PGC-1 coactivators in physiological and pathological conditions as well as the complex interplay of metabolic dysregulation and inflammation in obesity with special focus on skeletal muscle. We further put forward the hypothesis that, in this tissue, oxidative metabolism and inflammatory processes mutually antagonize each other. The nuclear factor κB (NF-κB) pathway thereby plays a key role in linking metabolic and inflammatory programs in muscle cells. We conclude this review with a perspective about the consequences of such a negative crosstalk on the immune system and the possibilities this opens for clinical applications

Measurements of neutrino oscillation parameters from the T2K experiment using 3.6×10213.6\times10^{21} protons on target

International audienceThe T2K experiment presents new measurements of neutrino oscillation parameters using $19.7(16.3)\times10^{20}$ protons on target (POT) in (anti-)neutrino mode at the far detector (FD). Compared to the previous analysis, an additional $4.7\times10^{20}$ POT neutrino data was collected at the FD. Significant improvements were made to the analysis methodology, with the near-detector analysis introducing new selections and using more than double the data. Additionally, this is the first T2K oscillation analysis to use NA61/SHINE data on a replica of the T2K target to tune the neutrino flux model, and the neutrino interaction model was improved to include new nuclear effects and calculations. Frequentist and Bayesian analyses are presented, including results on $\sin^2\theta_{13}$ and the impact of priors on the $\delta_\mathrm{CP}$ measurement. Both analyses prefer the normal mass ordering and upper octant of $\sin^2\theta_{23}$ with a nearly maximally CP-violating phase. Assuming the normal ordering and using the constraint on $\sin^2\theta_{13}$ from reactors, $\sin^2\theta_{23}=0.561^{+0.021}_{-0.032}$ using Feldman--Cousins corrected intervals, and $\Delta{}m^2_{32}=2.494_{-0.058}^{+0.041}\times10^{-3}~\mathrm{eV^2}$ using constant $\Delta\chi^{2}$ intervals. The CP-violating phase is constrained to $\delta_\mathrm{CP}=-1.97_{-0.70}^{+0.97}$ using Feldman--Cousins corrected intervals, and $\delta_\mathrm{CP}=0,\pi$ is excluded at more than 90% confidence level. A Jarlskog invariant of zero is excluded at more than $2\sigma$ credible level using a flat prior in $\delta_\mathrm{CP}$, and just below $2\sigma$ using a flat prior in $\sin\delta_\mathrm{CP}$. When the external constraint on $\sin^2\theta_{13}$ is removed, $\sin^2\theta_{13}=28.0^{+2.8}_{-6.5}\times10^{-3}$, in agreement with measurements from reactor experiments. These results are consistent with previous T2K analyses

First measurement of muon neutrino charged-current interactions on hydrocarbon without pions in the final state using multiple detectors with correlated energy spectra at T2K

This paper reports the first measurement of muon neutrino charged-current interactions without pions in the final state using multiple detectors with correlated energy spectra at T2K. The data was collected on hydrocarbon targets using the off-axis T2K near detector (ND280) and the on-axis T2K near detector (INGRID) with neutrino energy spectra peaked at 0.6 GeV and 1.1 GeV, respectively. The correlated neutrino flux presents an opportunity to reduce the impact of the flux uncertainty and to study the energy dependence of neutrino interactions. The extracted double-differential cross sections are compared to several Monte Carlo neutrino-nucleus interaction event generators showing the agreement between both detectors individually and with the correlated result