99 research outputs found

    Evaluation of the flame propagation within an SI engine using flame imaging and LES

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    This work shows experiments and simulations of the fired operation of a spark ignition engine with port-fuelled injection. The test rig considered is an optically accessible single cylinder engine specifically designed at TU Darmstadt for the detailed investigation of in-cylinder processes and model validation. The engine was operated under lean conditions using iso-octane as a substitute for gasoline. Experiments have been conducted to provide a sound database of the combustion process. A planar flame imaging technique has been applied within the swirl- and tumble-planes to provide statistical information on the combustion process to complement a pressure-based comparison between simulation and experiments. This data is then analysed and used to assess the large eddy simulation performed within this work. For the simulation, the engine code KIVA has been extended by the dynamically thickened flame model combined with chemistry reduction by means of pressure dependent tabulation. Sixty cycles have been simulated to perform a statistical evaluation. Based on a detailed comparison with the experimental data, a systematic study has been conducted to obtain insight into the most crucial modelling uncertainties

    Age-dependent increase of oxidative stress regulates microRNA-29 family preserving cardiac health.

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    The short-lived turquoise killifish Nothobranchius furzeri (Nfu) is a valid model for aging studies. Here, we investigated its age-associated cardiac function. We observed oxidative stress accumulation and an engagement of microRNAs (miRNAs) in the aging heart. MiRNA-sequencing of 5 week (young), 12-21 week (adult) and 28-40 week (old) Nfu hearts revealed 23 up-regulated and 18 down-regulated miRNAs with age. MiR-29 family turned out as one of the most up-regulated miRNAs during aging. MiR-29 family increase induces a decrease of known targets like collagens and DNA methyl transferases (DNMTs) paralleled by 5ÂŽmethyl-cytosine (5mC) level decrease. To further investigate miR-29 family role in the fish heart we generated a transgenic zebrafish model where miR-29 was knocked-down. In this model we found significant morphological and functional cardiac alterations and an impairment of oxygen dependent pathways by transcriptome analysis leading to hypoxic marker up-regulation. To get insights the possible hypoxic regulation of miR-29 family, we exposed human cardiac fibroblasts to 1% O <sub>2</sub> levels. In hypoxic condition we found miR-29 down-modulation responsible for the accumulation of collagens and 5mC. Overall, our data suggest that miR-29 family up-regulation might represent an endogenous mechanism aimed at ameliorating the age-dependent cardiac damage leading to hypertrophy and fibrosis

    Inhibition of fatty acid oxidation enables heart regeneration in adult mice

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    Postnatal maturation of cardiomyocytes is characterized by a metabolic switch from glycolysis to fatty acid oxidation, chromatin reconfiguration and exit from the cell cycle, instating a barrier for adult heart regeneration. Here, to explore whether metabolic reprogramming can overcome this barrier and enable heart regeneration, we abrogate fatty acid oxidation in cardiomyocytes by inactivation of Cpt1b. We find that disablement of fatty acid oxidation in cardiomyocytes improves resistance to hypoxia and stimulates cardiomyocyte proliferation, allowing heart regeneration after ischaemia-reperfusion injury. Metabolic studies reveal profound changes in energy metabolism and accumulation of α-ketoglutarate in Cpt1b-mutant cardiomyocytes, leading to activation of the α-ketoglutarate-dependent lysine demethylase KDM5. Activated KDM5 demethylates broad H3K4me3 domains in genes that drive cardiomyocyte maturation, lowering their transcription levels and shifting cardiomyocytes into a less mature state, thereby promoting proliferation. We conclude that metabolic maturation shapes the epigenetic landscape of cardiomyocytes, creating a roadblock for further cell divisions. Reversal of this process allows repair of damaged hearts

    Genome-Wide Identification of Small RNAs in the Opportunistic Pathogen Enterococcus faecalis V583

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    Small RNA molecules (sRNAs) are key mediators of virulence and stress inducible gene expressions in some pathogens. In this work we identify sRNAs in the Gram positive opportunistic pathogen Enterococcus faecalis. We characterized 11 sRNAs by tiling microarray analysis, 5â€Č and 3â€Č RACE-PCR, and Northern blot analysis. Six sRNAs were specifically expressed at exponential phase, two sRNAs were observed at stationary phase, and three were detected during both phases. Searches of putative functions revealed that three of them (EFA0080_EFA0081 and EFB0062_EFB0063 on pTF1 and pTF2 plasmids, respectively, and EF0408_EF04092 located on the chromosome) are similar to antisense RNA involved in plasmid addiction modules. Moreover, EF1097_EF1098 shares strong homologies with tmRNA (bi-functional RNA acting as both a tRNA and an mRNA) and EF2205_EF2206 appears homologous to 4.5S RNA member of the Signal Recognition Particle (SRP) ribonucleoprotein complex. In addition, proteomic analysis of the ΔEF3314_EF3315 sRNA mutant suggests that it may be involved in the turnover of some abundant proteins. The expression patterns of these transcripts were evaluated by tiling array hybridizations performed with samples from cells grown under eleven different conditions some of which may be encountered during infection. Finally, distribution of these sRNAs among genome sequences of 54 E. faecalis strains was assessed. This is the first experimental genome-wide identification of sRNAs in E. faecalis and provides impetus to the understanding of gene regulation in this important human pathogen

    A 1,000-loci transcript map of the barley genome: new anchoring points for integrative grass genomics

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    An integrated barley transcript map (consensus map) comprising 1,032 expressed sequence tag (EST)-based markers (total 1,055 loci: 607 RFLP, 190 SSR, and 258 SNP), and 200 anchor markers from previously published data, has been generated by mapping in three doubled haploid (DH) populations. Between 107 and 179 EST-based markers were allocated to the seven individual barley linkage groups. The map covers 1118.3 cM with individual linkage groups ranging from 130 cM (chromosome 4H) to 199 cM (chromosome 3H), yielding an average marker interval distance of 0.9 cM. 475 EST-based markers showed a syntenic organisation to known colinear linkage groups of the rice genome, providing an extended insight into the status of barley/rice genome colinearity as well as ancient genome duplications predating the divergence of rice and barley. The presented barley transcript map is a valuable resource for targeted marker saturation and identiWcation of candidate genes at agronomically important loci. It provides new anchor points for detailed studies in comparative grass genomics and will support future attempts towards the integration of genetic and physical mapping information
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