Role of Esrrg in the Fibrate-Mediated Regulation of Lipid Metabolism Genes in Human ApoA-I Transgenic Mice

We have used a new ApoA-I transgenic mouse model to identify by global gene expression profiling, candidate genes that affect lipid and lipoprotein metabolism in response to fenofibrate treatment. Multilevel bioinformatical analysis and stringent selection criteria (2-fold change, 0% false discovery rate) identified 267 significantly changed genes involved in several molecular pathways. The fenofibrate-treated group did not have significantly altered levels of hepatic human APOA-I mRNA and plasma ApoA-I compared with the control group. However, the treatment increased cholesterol levels to 1.95-fold mainly due to the increase in high-density lipoprotein (HDL) cholesterol. The observed changes in HDL are associated with the upregulation of genes involved in phospholipid biosynthesis and lipid hydrolysis, as well as phospholipid transfer protein. Significant upregulation was observed in genes involved in fatty acid transport and β-oxidation, but not in those of fatty acid and cholesterol biosynthesis, Krebs cycle and gluconeogenesis. Fenofibrate changed significantly the expression of seven transcription factors. The estrogen receptor-related gamma gene was upregulated 2.36-fold and had a significant positive correlation with genes of lipid and lipoprotein metabolism and mitochondrial functions, indicating an important role of this orphan receptor in mediating the fenofibrate-induced activation of a specific subset of its target genes.National Institutes of Health (HL48739 and HL68216); European Union (LSHM-CT-2006-0376331, LSHG-CT-2006-037277); the Biomedical Research Foundation of the Academy of Athens; the Hellenic Cardiological Society; the John F Kostopoulos Foundatio

Universal architecture of bacterial chemoreceptor arrays

Chemoreceptors are key components of the high-performance signal transduction system that controls bacterial chemotaxis. Chemoreceptors are typically localized in a cluster at the cell pole, where interactions among the receptors in the cluster are thought to contribute to the high sensitivity, wide dynamic range, and precise adaptation of the signaling system. Previous structural and genomic studies have produced conflicting models, however, for the arrangement of the chemoreceptors in the clusters. Using whole-cell electron cryo-tomography, here we show that chemoreceptors of different classes and in many different species representing several major bacterial phyla are all arranged into a highly conserved, 12-nm hexagonal array consistent with the proposed “trimer of dimers” organization. The various observed lengths of the receptors confirm current models for the methylation, flexible bundle, signaling, and linker sub-domains in vivo. Our results suggest that the basic mechanism and function of receptor clustering is universal among bacterial species and was thus conserved during evolution

Four cycles of paclitaxel and carboplatin as adjuvant treatment in early-stage ovarian cancer: a six-year experience of the Hellenic Cooperative Oncology Group

BACKGROUND: Surgery can cure a significant percentage of ovarian carcinoma confined to the pelvis. Nevertheless, there is still a 10–50% recurrence rate. We administered paclitaxel/carboplatin as adjuvant treatment in early-stage ovarian carcinoma. METHODS: Patients with stages Ia or Ib, Grade 2 or 3 and Ic to IIb (any grade) were included. Patients were treated with 4 cycles of Paclitaxel 175 mg/m(2 )and Carboplatin [area under the curve (AUC) 6 (Calvert Formula)] every 3 weeks. RESULTS: Sixty-nine patients with no residual disease following cytoreductive surgery and minimal or modified surgical staging were included in this analysis. Grade 3 or 4 neutropenia occured in 29.9% of patients, while neutropenic fever was reported in 4.5%. Neurotoxicity (all Grade 1 or 2) was reported in 50% of cases. Median follow-up was 62 months. 5-year overall survival (OS) and relapse-free survival (RFS) were: 87% (95% confidence intervals [CI]: 78–96) and 79% (95% CI: 69–89), respectively. Significantly fewer patients with stages Ic-IIb and tumor grade 2 or 3 achieved a 5-year RFS than patients with only one of these two factors (73% vs 92%, p = 0.03). CONCLUSION: Paclitaxel/Carboplatin chemotherapy is a safe and effective adjuvant treatment in early-stage ovarian carcinoma. Patients with stages Ic-IIb and tumor grade 2 or 3 may benefit from more extensive treatment

The distribution of inverted repeat sequences in the Saccharomyces cerevisiae genome

Although a variety of possible functions have been proposed for inverted repeat sequences (IRs), it is not known which of them might occur in vivo. We investigate this question by assessing the distributions and properties of IRs in the Saccharomyces cerevisiae (SC) genome. Using the IRFinder algorithm we detect 100,514 IRs having copy length greater than 6 bp and spacer length less than 77 bp. To assess statistical significance we also determine the IR distributions in two types of randomization of the S. cerevisiae genome. We find that the S. cerevisiae genome is significantly enriched in IRs relative to random. The S. cerevisiae IRs are significantly longer and contain fewer imperfections than those from the randomized genomes, suggesting that processes to lengthen and/or correct errors in IRs may be operative in vivo. The S. cerevisiae IRs are highly clustered in intergenic regions, while their occurrence in coding sequences is consistent with random. Clustering is stronger in the 3′ flanks of genes than in their 5′ flanks. However, the S. cerevisiae genome is not enriched in those IRs that would extrude cruciforms, suggesting that this is not a common event. Various explanations for these results are considered

Removal of zinc from aqueous systems using enhanced micellar ultrafiltration (MEUF)

Στην παρούσα διπλωματική διατριβή μελετήθηκε η απομάκρυνση του ψευδαργύρου (Zn2+) από υδατικά συστήματα με τη χρήση ενισχυμένης υπερδιήθησης (MEUF) ως μέθοδο διαχωρισμού. Τα πεδία εφαρμογών της υπερδιήθησης ή της ενισχυμένης υπερδιήθησης μέσω μικκυλίων τασιενεργών (ΕΥΜΜ - micellar enhanced ultrafiltration - MEUF) είναι η απομάκρυνση επιφανειακά ενεργών ενώσεων (π. χ. απορρυπαντικών) από υδατικά διαλύματα, η απομάκρυνση οργανικών και ανόργανων ενώσεων μέσω του εγκλωβισμού τους σε μικκύλια τασιενεργών και η ανάκτηση των τασιενεργών από την εφαρμογή της πλημμυρίδας τασιενεργών για την εξυγίανση εδαφών (Surfactant Enhanced Remediation). Η εργασία αυτή περιελάμβανε πειράματα υπερδιήθησης εφαπτομενικής ροής (crossflow ultrafiltration) με διαλύματα μικκυλίων τασιενεργού περιέχοντα το ρύπο Ζn2+ Χρησιμοποιήθηκαν μεμβράνες πολυσουλφόνης και οξικής κυτταρίνης με ονομαστικό cut-off 5.000,10.000 και 30.000. Τα τασιενεργά που χρησιμοποιήθηκαν στην παρούσα διατριβή ήταν: Συμβατικα προερχόμενα κυρίως από τα πετροχημικά, του τύπου των αιθοξυλιωμένων λιπαρών αλκοολών και φαινολών με διαφορετικό αριθμό αιθυλενοξιδίων. Εξετάστηκαν δύο ομάδες με τα εμπορικά ονοόματα Neodol (91-5Ε,91-6Ε,91-8Ε) και TRITON (X100,X102,X114) και εκτιμήθηκαν οι παράμετροι ροής (μείωση ροής, ανάκτηση ροής) σε διαμεμβρανική πίεση P=2bar και Τ= 20οC Μη συμβατικά: Oι ζαχαροεστέρες L1695 και S1670. H αξιολόγηση της αποτελεσματικότητας των μεμβρανών που χρησιμοποιήθηκαν, σε συνδυασμό με το είδος των μικκυλίων των τασιενεργών βασίστηκε στα αποτελέσματα ροής και συγκέντρωσης των τασιενεργών και ψευδαργύρου στο πέρασμα (permeate). Κατά την ανάλυση των πειραματικών δεδομένων παρατηρήθηκε η καλύτερη συμπεριφορά του ζαχαροεστέρα L1695, ο οποίος παρουσίασε υψηλή απομάκρυνση ρύπου τόσο στις μεμβράνες πολυσουλφόνης οσο και σε αυτές της οξικής κυτταρίνης . Η αναλυτική μέθοδος που χρησιμοποιήθηκε για τον προσδιορισμό της συγκράτησης του Zn ήταν η φασματομετρία ατομικής απορρόφησης (ΑΑS).The aim of this study was the the removal of zinc (Zn2 +) from aqueous systems using enhanced micellar ultrafiltration (MEUF) as a method of separation. The applications of ultrafiltration or enhanced ultrafiltration through micelle surfactants (ΜEUF - micellar enhanced ultrafiltration) include the removal of surface active compounds from aqueous solutions, the retention of organic and inorganic compounds through entrapment in micelle and the recovery of surfactants during flood remediation soils (Surfactant Enhanced Remediation). The examination of ultrafiltration comprises tangential flow ultrafiltration experiments (crossflow ultrafiltration) with solutions containing surfactant micelle and the Zn2 + as pollutant. In this study polysulfone and cellulose acetate membranes were used with a nominal cut-off 5.000,10.000 and 30,000. The surfactants used in this thesis were: • Conventional: Neodol 91-5E ,91-6E ,91-8E and TRITON X100, X102, X114 • Non-conventional: Sugaresters S1670 and L1695. The flow parameter (flux reduction, flux recovery) as well as zinc concentration in permeate were estimated. L1695 sugar ester was proved most effective pollutant removal on both membranes.Δημήτριος Ι. Ζάννη

Effect of apoA-I Mutations in the Capacity of Reconstituted HDL to Promote ABCG1-Mediated Cholesterol Efflux.

ATP binding cassette transporter G1 (ABCG1) mediates the cholesterol transport from cells to high-density lipoprotein (HDL), but the role of apolipoprotein A-I (apoA-I), the main protein constituent of HDL, in this process is not clear. To address this, we measured cholesterol efflux from HEK293 cells or J774 mouse macrophages overexpressing ABCG1 using as acceptors reconstituted HDL (rHDL) containing wild-type or various mutant apoA-I forms. It was found that ABCG1-mediated cholesterol efflux was severely reduced (by 89%) when using rHDL containing the carboxyl-terminal deletion mutant apoA-I[Δ(185-243)]. ABCG1-mediated cholesterol efflux was not affected or moderately decreased by rHDL containing amino-terminal deletion mutants and several mid-region deletion or point apoA-I mutants, and was restored to 69-99% of control by double deletion mutants apoA-I[Δ(1-41)Δ(185-243)] and apoA-I[Δ(1-59)Δ(185-243)]. These findings suggest that the central helices alone of apoA-I associated to rHDL can promote ABCG1-mediated cholesterol efflux. Further analysis showed that rHDL containing the carboxyl-terminal deletion mutant apoA-I[Δ(185-243)] only slightly reduced (by 22%) the ABCG1-mediated efflux of 7-ketocholesterol, indicating that depending on the sterol type, structural changes in rHDL-associated apoA-I affect differently the ABCG1-mediated efflux of cholesterol and 7-ketocholesterol. Overall, our findings demonstrate that rHDL-associated apoA-I structural changes affect the capacity of rHDL to accept cellular cholesterol by an ABCG1-mediated process. The structure-function relationship seen here between rHDL-associated apoA-I mutants and ABCG1-mediated cholesterol efflux closely resembles that seen before in lipid-free apoA-I mutants and ABCA1-dependent cholesterol efflux, suggesting that both processes depend on the same structural determinants of apoA-I