Mitochondrial Fatty Acid β-Oxidation Disorders: From Disease to Lipidomic Studies—A Critical Review

ReviewThis article belongs to the Special Issue Lipid Metabolism in Pathology and Health.Fatty acid oxidation disorders (FAODs) are inborn errors of metabolism (IEMs) caused by defects in the fatty acid (FA) mitochondrial β-oxidation. The most common FAODs are characterized by the accumulation of medium-chain FAs and long-chain (3-hydroxy) FAs (and their carnitine derivatives), respectively. These deregulations are associated with lipotoxicity which affects several organs and potentially leads to life-threatening complications and comorbidities. Changes in the lipidome have been associated with several diseases, including some IEMs. In FAODs, the alteration of acylcarnitines (CARs) and FA profiles have been reported in patients and animal models, but changes in polar and neutral lipid profile are still scarcely studied. In this review, we present the main findings on FA and CAR profile changes associated with FAOD pathogenesis, their correlation with oxidative damage, and the consequent disturbance of mitochondrial homeostasis. Moreover, alterations in polar and neutral lipid classes and lipid species identified so far and their possible role in FAODs are discussed. We highlight the need of mass-spectrometry-based lipidomic studies to understand (epi)lipidome remodelling in FAODs, thus allowing to elucidate the pathophysiology and the identification of possible biomarkers for disease prognosis and an evaluation of therapeutic efficacy.This research was funded by FCT/MEC (PIDDAC) for their financial support to LAQVREQUIMTE (UIDB/50006/2020), CESAM (UIDP/50017/2020 + UIDB/50017/2020 + LA/P/0094/2020), and the RNEM-Portuguese Mass Spectrometry Network (LISBOA-01-0145-FEDER-402-022125), financed by FCT/MCTES through national funds and, where applicable, co-financed by the FEDER, within the PT2020 Partnership Agreement and Compete 2020. Ana Moreira thanks the research contract under the research unit LAQV-REQUIMTE. Inês M. S. Guerra (2021.04754.BD) and Helena B. Ferreira (2020.04611.BD) are grateful to FCT for the PhD grants. Tânia Melo thanks the Junior Researcher contract in the scope of the Individual Call to Scientific Employment Stimulus 2020 (CEECIND/01578/2020). The authors are thankful to the COST Action EpiLipidNET, CA19105-Pan-European Network in Lipidomics, and EpiLipidomics.info:eu-repo/semantics/publishedVersio

The check of QCD based on the tau-decay data analysis in the complex q^2-plane

The thorough analysis of the ALEPH data on hadronic tau-decay is performed in the framework of QCD. The perturbative calculations are performed in 3 and 4-loop approximations. The terms of the operator product expansion (OPE) are accounted up to dimension D=8. The value of the QCD coupling constant alpha_s(m_tau^2)=0.355 pm 0.025 was found from hadronic branching ratio R_tau. The V+A and V spectral function are analyzed using analytical properties of polarization operators in the whole complex q^2-plane. Borel sum rules in the complex q^2 plane along the rays, starting from the origin, are used. It was demonstrated that QCD with OPE terms is in agreement with the data for the coupling constant close to the lower error edge alpha_s(m_tau^2)=0.330. The restriction on the value of the gluonic condensate was found =0.006 pm 0.012 GeV^2. The analytical perturbative QCD was compared with the data. It is demonstrated to be in strong contradiction with experiment. The restrictions on the renormalon contribution were found. The instanton contributions to the polarization operator are analyzed in various sum rules. In Borel transformation they appear to be small, but not in spectral moments sum rules.Comment: 24 pages; 1 latex + 13 figure files. V2: misprints are corrected, uncertainty in alpha_s is explained in more transparent way, acknowledgement is adde

Identification of phenolic constituents of cytisus multiflorus

The phenolic composition of the ethanolic extract obtained from the flowers of the medicinal plant Cytisus multiflorus has been elucidated by high performance liquid chromatography, electrospray mass spectrometry and nuclear magnetic resonance analysis. The extract was mainly composed of flavones, including the common chrysin, orientin, luteolin-5-O-glucoside, luteolin-7-O-glucoside, apigenin and apigenin-7-O-glucoside, which appeared as minor components. The major flavone in the extract was chrysin-7-O-B-D-glucopyranoside, and it also contained moderate amounts of a dihydroxyflavone isomer of chrysin, as well as of 2''-O-pentosyl-6-C-hexosyl-luteolin, 2''-O-pentosyl-8-C-hexosyl-luteolin and 6''- O-(3-hydroxy-3-methylglutaroyl)-2''-O-pentosyl-C-hexosyl-apigenin, which are not commonly found in the Fabaceae family. Other novel phenolic compounds found in the ethanolic extract of C. multiflorus comprised the flavones 2''-O-pentosyl-6-C-hexosyl-apigenin, 2''-O-pentosyl-8-C-hexosyl-apigenin and 6''-O-(3-hydroxy-3-methylglutaroyl)-200-O-pentosyl-C-hexosyl-luteolin. The assessment of the biological activities of the main compounds of this extract are now keen, in order to determine their relevance in the beneficial properties of the plant

Vitamin E-analog Trolox prevents endoplasmic reticulum stress in frozen-thawed ovarian tissue of capuchin monkey (Sapajus apella)

Ovarian fragments were exposed to 0.5 M sucrose and 1 M ethylene glycol (freezing solution; FS) with or without selenium or Trolox. Histological and ultrastructural analyses showed that the percentages of normal follicles in control tissue and in tissue after exposure to FS+50 μM Trolox were similar. Trolox prevented endoplasmic reticulum (ER)-related vacuolization, which is commonly observed in oocytes and stromal tissue after exposure to FS. From the evaluated stress markers, superoxide dismutase 1 (SOD1) was up-regulated in ovarian tissue exposed to FS+10 ng/ml selenium. Ovarian fragments were subsequently frozenthawed in the presence of FS with or without 50 μM Trolox, followed by in vitro culture (IVC). Antioxidant capacity in ovarian fragments decreased after freeze-thawing in Troloxfree FS compared with FS+50 μMTrolox. Although freezing itself minimized the percentage of viable follicles in each solution, Trolox supplementation resulted in higher rates of viable follicles (67 %), even after IVC (61 %). Furthermore, stress markers SOD1 and ERp29 were up-regulated in ovarian tissue frozen-thawed in Trolox-free medium. Relative mRNA expression of growth factors markers was evaluated after freeze-thawing followed by IVC. BMP4, BMP5, CTGF, GDF9 and KL were down-regulated independently of the presence of Trolox in FS but down-regulation was less pronounced in the presence of Trolox. Thus, medium supplementation with 50 μMTrolox prevents ER stress and, consequently, protects ovarian tissue from ER-derived cytoplasmic vacuolization. ERp29 but not ERp60, appears to be a key marker linking stress caused by freezing-thawing and cell vacuolization.http://link.springer.com/journal/441hb201

Studies of the Cabbibo-Suppressed Decays D+→π0ℓ+νD^+ \to \pi^0 \ell^+ \nu and D+→ηe+νeD^+ \to \eta e^+ \nu_e

Using 4.8 fb$^{-1}$ of data taken with the CLEO II detector, the branching fraction for the Cabibbo-suppressed decay $D^+\to\pi^0\ell^+\nu$ measured relative to the Cabibbo favored decay $D^+\to\bar{K^0}\ell^+\nu$ is found to be $0.046\pm 0.014\pm 0.017$. Using $V_{cs}$ and $V_{cd}$ from unitarity constraints, we determine $| f_+^{\pi}(0)/f_+^K(0)|^2=0.9\pm 0.3\pm 0.3$ We also present a 90% confidence level upper limit for the branching ratio of the decay $D^+ \to \eta e^+\nu_e$ relative to that for $D^+ \to \pi^0 e^+\nu_e$ of 1.5.Comment: 10 page postscript file, postscript file also available through http://w4.lns.cornell.edu/public/CLN

Oviposição do curuquerê e alimentação de suas lagartas neonatas em algodoeiros tratados com caulim

Resumo: O objetivo deste trabalho foi avaliar a capacidade do caulim de afetar a oviposição e a alimentação de Alabama argillacea (Lepidoptera: Noctuidae) em algodoeiro. Determinou-se a preferência de oviposição, a viabilidade de ovos e o consumo das lagartas de primeiro instar de A. argillacea, em folhas de algodão tratadas ou não com caulim. A preferência de oviposição foi determinada por teste de escolha e confinamento, em delineamento experimental de blocos ao acaso, em arranjo fatorial 2x7, representado pelos tratamentos com caulim em água destilada (60 g L-1) ou somente água destilada (testemunha), e pela avaliação de sete estruturas vegetais da planta. O consumo pelas lagartas de primeiro instar foi determinado em delineamento experimental inteiramente casualizado, em arranjo fatorial 2x4, representado pelo tratamento com caulim em água destilada, pela testemunha e pelos quatro períodos de observação (6, 12, 24 e 48 horas). A oviposição das mariposas do curuquerê-do-algodoeiro foi reduzida nas plantas de algodão tratadas com caulim; no entanto, a viabilidade dos ovos não foi afetada. A folha da haste foi a estrutura preferida para oviposição. A sobrevivência e o consumo de lagartas de primeiro instar do curuquerê são menores nas plantas de algodão tratadas com caulim