1.Omega-9 Oleic Acid Induces Fatty Acid Oxidation and Decreases Organ Dysfunction and Mortality in Experimental Sepsis.
Gonçalves-de-Albuquerque CF1, Medeiros-de-Moraes IM1, Oliveira FM1, Burth P2, Bozza PT1, Castro Faria MV3, Silva AR1, Castro-Faria-Neto HC1,4. PLoS One. 2016 Apr 14;11(4):e0153607. doi: 10.1371/journal.pone.0153607.
Sepsis is characterized by inflammatory and metabolic alterations, which lead to massive cytokine production, oxidative stress and organ dysfunction. In severe systemic inflammatory response syndrome, plasma non-esterified fatty acids (NEFA) are increased. Several NEFA are deleterious to cells, activate Toll-like receptors and inhibit Na+/K+-ATPase, causing lung injury. A Mediterranean diet rich in olive oil is beneficial. The main component of olive oil is omega-9 oleic acid (OA), a monounsaturated fatty acid (MUFA). We analyzed the effect of OA supplementation on sepsis. OA ameliorated clinical symptoms, increased the survival rate, prevented liver and kidney injury and decreased NEFA plasma levels in mice subjected to cecal ligation and puncture (CLP). OA did not alter food intake and weight gain but diminished reactive oxygen species (ROS) production and NEFA plasma levels. Carnitine palmitoyltransferase IA (CPT1A) mRNA levels were increased, while uncoupling protein 2 (UCP2) liver expression was enhanced in mice treated with OA.
2.Histone deacetylase inhibitor-induced cancer stem cells exhibit high pentose phosphate pathway metabolism.
Debeb BG1,2, Lacerda L1,2, Larson R1,2, Wolfe AR1,2, Krishnamurthy S3,2, Reuben JM4,2, Ueno NT5,2, Gilcrease M3, Woodward WA1,2. Oncotarget. 2016 Apr 7. doi: 10.18632/oncotarget.8631. [Epub ahead of print]
PURPOSE: We recently demonstrated that histone deacetylase (HDAC) inhibitors can "reprogram" differentiated triple-negative breast cancer cells to become quiescent stem-like cancer cells. We hypothesized that the metabolic state of such cells differs from that of their differentiated progeny.
3.PPARγ Is Activated during Congenital Cytomegalovirus Infection and Inhibits Neuronogenesis from Human Neural Stem Cells.
Rolland M1, Li X2, Sellier Y3,4, Martin H1, Perez-Berezo T1, Rauwel B1, Benchoua A5,6, Bessières B3,4, Aziza J7, Cenac N1, Luo M2, Casper C1,8, Peschanski M5,6, Gonzalez-Dunia D1, Leruez-Ville M3,4, Davrinche C1, Chavanas S1. PLoS Pathog. 2016 Apr 14;12(4):e1005547. doi: 10.1371/journal.ppat.1005547. eCollection 2016.
Congenital infection by human cytomegalovirus (HCMV) is a leading cause of permanent sequelae of the central nervous system, including sensorineural deafness, cerebral palsies or devastating neurodevelopmental abnormalities (0.1% of all births). To gain insight on the impact of HCMV on neuronal development, we used both neural stem cells from human embryonic stem cells (NSC) and brain sections from infected fetuses and investigated the outcomes of infection on Peroxisome Proliferator-Activated Receptor gamma (PPARγ), a transcription factor critical in the developing brain. We observed that HCMV infection dramatically impaired the rate of neuronogenesis and strongly increased PPARγ levels and activity. Consistent with these findings, levels of 9-hydroxyoctadecadienoic acid (9-HODE), a known PPARγ agonist, were significantly increased in infected NSCs. Likewise, exposure of uninfected NSCs to 9-HODE recapitulated the effect of infection on PPARγ activity.
4.Initiation of RNA Polymerization and Polymerase Encapsidation by a Small dsRNA Virus.
Collier AM1, Lyytinen OL2, Guo YR1, Toh Y1, Poranen MM2, Tao YJ1. PLoS Pathog. 2016 Apr 14;12(4):e1005523. doi: 10.1371/journal.ppat.1005523. eCollection 2016.
During the replication cycle of double-stranded (ds) RNA viruses, the viral RNA-dependent RNA polymerase (RdRP) replicates and transcribes the viral genome from within the viral capsid. How the RdRP molecules are packaged within the virion and how they function within the confines of an intact capsid are intriguing questions with answers that most likely vary across the different dsRNA virus families. In this study, we have determined a 2.4 Å resolution structure of an RdRP from the human picobirnavirus (hPBV). In addition to the conserved polymerase fold, the hPBV RdRP possesses a highly flexible 24 amino acid loop structure located near the C-terminus of the protein that is inserted into its active site. In vitro RNA polymerization assays and site-directed mutagenesis showed that: (1) the hPBV RdRP is fully active using both ssRNA and dsRNA templates; (2) the insertion loop likely functions as an assembly platform for the priming nucleotide to allow de novo initiation; (3) RNA transcription by the hPBV RdRP proceeds in a semi-conservative manner; and (4) the preference of virus-specific RNA during transcription is dictated by the lower melting temperature associated with the terminal sequences.