On the Lx-L6micron ratio as a diagnostic for Compton-thick AGN

As the mid-IR luminosity represents a good isotropic proxy of the AGN power, a low X-ray to mid-IR luminosity ratio is often claimed to be a reliable indicator for selecting Compton-thick (CT) AGN. We assess the efficiency of this diagnostic by examining the 12mu IRAS AGN sample for which high signal-to-noise XMM observations have been recently become available. We find that the vast majority (10/11) of the AGN that have been classified as CT on the basis the X-ray spectroscopy by Brightman & Nandra present a low Lx/L6 luminosity ratio, i.e. lower than a few percent of the average AGN ratio which is typical of reflection-dominated CT sources. At low Lx/L6 ratios we also find a comparable number of AGN, most of which are heavily absorbed but not CT. This implies that although most Compton-thick AGN present low Lx/L6 ratios, at least in the local, Universe, the opposite is not necessarily true. Next, we extend our analysis to higher redshifts. We perform the same analysis in the CDFS where excellent quality chandra (4 Ms) and xmm (3 Ms) X-ray spectra are available. We derive accurate X-ray luminosities for chandra sources using X-ray spectral fits, as well as 6mu luminosities from SED fits. We find 8 AGN with low Lx/L6 ratios in total, after excluding one source where the 6mu emission primarily comes from star-formation. One of these sources has been already demonstrated to host a CT nucleus, while for another one at a redshift of z=1.22 we argue it is most likely CT on the basis of its combined chandra and xmm spectrum. We find a large number of non CT contaminant with low Lx/L6 ratios. The above suggest that a low Lx/L6 ratio alone cannot ascertain the presence of a CT AGN, albeit the majority of low Lx/L6 AGN are heavily obscured. The two most reliable CT AGN in the high redshift Universe have high Lx/L6 ratios, showing that this method cannot provide complete CT AGN samples.Comment: 11 pages, to appear to A&

Synthesis of a series of 16, 16-dimethyl-prostacyclin and 6-keto prostaglandin analogs, 1978

A synthesis is described for a number of 16,16-dimethyl analogs of the prostacyclin and related 6-keto prostaglandin types. Included are l6, l6-dimethyl-PGI2 sodium salt (XLIV), 6?-l6, l6-dimethyl-PGI1(XLV), 6?-l6, l6-dimethyl-PGI1 (XLVII), 6-keto-l6, l6-dimethyl-PGF1-? (XLIX), and 6-keto-l6, l6-dimethyl PGE1 (LV). Done, but not included, is the activity for these analogs in the blood platelet aggregation inhibition assay. This activity was consistently less than for the corresponding 16, 16-dihydro compounds

Involvement of ribosomal protein L6 in assembly of functional 50S ribosomal subunit in Escherichia coli cells

Ribosomal protein L6, an essential component of the large (50S) subunit, primarily binds to helix 97 of 23S rRNA and locates near the sarcin/ricin loop of helix 95 that directly interacts with GTPase translation factors. Although L6 is believed to play important roles in factor-dependent ribosomal function, crucial biochemical evidence for this hypothesis has not been obtained. We constructed and characterized an Escherichia coli mutant bearing a chromosomal L6 gene (rplF) disruption and carrying a plasmid with an arabinose-inducible L6 gene. Although this ﾎ猫6 mutant grew more slowly than its wild-type parent, it proliferated in the presence of arabinose. Interestingly, cell growth in the absence of arabinose was biphasic. Early growth lasted only a few generations (LI-phase) and was followed by a suspension of growth for several hours (S-phase). This suspension was followed by a second growth phase (LII-phase). Cells harvested at both LI- and S-phases contained ribosomes with reduced factor-dependent GTPase activity and accumulated 50S subunit precursors (45S particles). The 45S particles completely lacked L6. Complete 50S subunits containing L6 were observed in all growth phases regardless of the L6-depleted condition, implying that the ﾎ猫6 mutant escaped death because of a leaky expression of L6 from the complementing plasmid. We conclude that L6 is essential for the assembly of functional 50S subunits at the late stage. We thus established conditions for the isolation of L6-depleted 50S subunits, which are essential to study the role of L6 in translation.ArticleBiochemical and Biophysical Research Communications.473(1):237-242(2016)journal articl

Screening and Identification of Disaccharides with Insulin Mimetic Activity against L6 Cells

Insulin mimetics are considered as prospective anti-diabetic agents, and the disaccharide, neohesperidose, has been found to show insulin mimetic activity against L6 cells. We screened several other disaccharides for their insulin mimetic activity and identified three new insulin mimetic disaccharides

ENPP1 Affects Insulin Action and Secretion: Evidences from In Vitro Studies

The aim of this study was to deeper investigate the mechanisms through which ENPP1, a negative modulator of insulin receptor (IR) activation, plays a role on insulin signaling, insulin secretion and eventually glucose metabolism. ENPP1 cDNA (carrying either K121 or Q121 variant) was transfected in HepG2 liver-, L6 skeletal muscle- and INS1E beta-cells. Insulin-induced IR-autophosphorylation (HepG2, L6, INS1E), Akt-Ser473, ERK1/2-Thr202/Tyr204 and GSK3-beta Ser9 phosphorylation (HepG2, L6), PEPCK mRNA levels (HepG2) and 2-deoxy-D-glucose uptake (L6) was studied. GLUT 4 mRNA (L6), insulin secretion and caspase-3 activation (INS1E) were also investigated. Insulin-induced IR-autophosphorylation was decreased in HepG2-K, L6-K, INS1E-K (20%, 52% and 11% reduction vs. untransfected cells) and twice as much in HepG2-Q, L6-Q, INS1E-Q (44%, 92% and 30%). Similar data were obtained with Akt-Ser473, ERK1/2-Thr202/Tyr204 and GSK3-beta Ser9 in HepG2 and L6. Insulin-induced reduction of PEPCK mRNA was progressively lower in untransfected, HepG2-K and HepG2-Q cells (65%, 54%, 23%). Insulin-induced glucose uptake in untransfected L6 (60% increase over basal), was totally abolished in L6-K and L6-Q cells. GLUT 4 mRNA was slightly reduced in L6-K and twice as much in L6-Q (13% and 25% reduction vs. untransfected cells). Glucose-induced insulin secretion was 60% reduced in INS1E-K and almost abolished in INS1E-Q. Serum deficiency activated caspase-3 by two, three and four folds in untransfected INS1E, INS1E-K and INS1E-Q. Glyburide-induced insulin secretion was reduced by 50% in isolated human islets from homozygous QQ donors as compared to those from KK and KQ individuals. Our data clearly indicate that ENPP1, especially when the Q121 variant is operating, affects insulin signaling and glucose metabolism in skeletal muscle- and liver-cells and both function and survival of insulin secreting beta-cells, thus representing a strong pathogenic factor predisposing to insulin resistance, defective insulin secretion and glucose metabolism abnormalities

L6 skeletal muscle cells have functional V1-vasopressin receptors coupled to stimulated inositol phospholipid metabolism

AbstractThe effects of vasopressin and related peptides upon the rat skeletal muscle cell line, L6, have been examined. No effects upon cellular cyclic AMP levels were found indicating that L6 cells possess no functional V2-vasopressin receptors. Vasopressin and its analogues did, however, stimulate the rapid and dose-dependent accumulation of inositol phosphates. This effect and the rank order of potency of vasopressin analogues demonstrate the presence of functional V1-vasopressin receptors upon L6 cells. These results suggest that the L6 line may be a useful model for vasopressin effects upon skeletal muscle metabolism

Constitutive Expression of Insulin Receptor Substrate (IRS)-1 Inhibits Myogenic Differentiation through Nuclear Exclusion of Foxo1 in L6 Myoblasts

Insulin-like growth factors (IGFs) are well known to play essential roles in enhancement of myogenic differentiation. In this report we showed that initial IGF-I signal activation but long-term IGF-1 signal termination are required for myogenic differentiation. L6 myoblast stably transfected with myc-epitope tagged insulin receptor substrate-1, myc-IRS-1 (L6-mIRS1) was unable to differentiate into myotubes, indicating that IRS-1 constitutive expression inhibited myogenesis. To elucidate the molecular mechanisms underlying myogenic inhibition, IGF-I signaling was examined. IGF-I treatment of control L6 cells for 18 h resulted in a marked suppression of IGF-I stimulated IRS-1 association with the p85 PI 3-kinase and suppression of activation of Akt that correlated with a down regulation of IRS-1 protein. L6-mIRS1 cells, in contrast, had sustained high levels of IRS-1 protein following 18 h of IGF-I treatment with persistent p85 PI 3-kinase association with IRS-1, Akt phosphorylation and phosphorylation of the downstream Akt substrate, Foxo1. Consistent with Foxo1 phosphorylation, Foxo1 protein was excluded from the nuclei in L6-mIRS1 cells, whereas Foxo1 was localized in the nuclei in control L6 cells during induction of differentiation. In addition, L6 cells stably expressing a dominant-interfering form of Foxo1, Δ256Foxo1 (L6-Δ256Foxo1) were unable to differentiate into myotubes. Together, these data demonstrate that IGF-I regulation of Foxo1 nuclear localization is essential for the myogenic program in L6 cells but that persistent activation of IGF-1 signaling pathways results in a negative feedback to prevent myogenesis

Comparative genomics of Mycobacterium africanum Lineage 5 and Lineage 6 from Ghana suggests distinct ecological niches.

Mycobacterium africanum (Maf) causes a substantial proportion of human tuberculosis in some countries of West Africa, but little is known on this pathogen. We compared the genomes of 253 Maf clinical isolates from Ghana, including N = 175 Lineage 5 (L5) and N = 78 Lineage 6 (L6). We found that the genomic diversity of L6 was higher than in L5 despite the smaller sample size. Regulatory proteins appeared to evolve neutrally in L5 but under purifying selection in L6. Even though over 90% of the human T cell epitopes were conserved in both lineages, L6 showed a higher ratio of non-synonymous to synonymous single nucleotide variation in these epitopes overall compared to L5. Of the 10% human T cell epitopes that were variable, most carried mutations that were lineage-specific. Our findings indicate that Maf L5 and L6 differ in some of their population genomic characteristics, possibly reflecting different selection pressures linked to distinct ecological niches

Impact of Early Loss of Lower First Permanent Molars on Third Molar Development and Position

Objective: To evaluate the effects of unilateral loss of the lower first permanent molar (L6) on the position and development of the lower third molar (L8). Material and Methods: Fifty-four panoramic radiographs of subjects with unilateral loss of L6 were examined. The L8 on the side of the L6 loss was compared with the L8 in the hemiarch without L6 loss (contralateral). The effect of L6 loss on the positioning of L8 was examined in all the samples (n=54), whereas the effect on the development of the third molar was examined in 38 patients with L8 with incomplete root formation. The Signs statistical test was used to evaluate the comparison between loss and contralateral hemiarches. Results: In 20 (37%) of 54 subjects, the L8 was better positioned in the hemiarch with loss of the lower first molar (p<0.001) compared with the control side. In the remaining 34 subjects, no difference was found. When only the L8 considered as impacted on the control side was examined (n=30), the cases with better positioning on the side with L6 loss increased to 66.6% (p<0.001). Conclusion: The loss of lower first molars improves the position of the lower third molar during its active eruption, mainly when the lower third molar is impacted. However, L6 loss does not affect the root development of lower third molars

Impact of Early Loss of Lower First Permanent Molars on Third Molar Development and Position

Objective: To evaluate the effects of unilateral loss of the lower first permanent molar (L6) on the position and development of the lower third molar (L8). Material and Methods: Fifty-four panoramic radiographs of subjects with unilateral loss of L6 were examined. The L8 on the side of the L6 loss was compared with the L8 in the hemiarch without L6 loss (contralateral). The effect of L6 loss on the positioning of L8 was examined in all the samples (n=54), whereas the effect on the development of the third molar was examined in 38 patients with L8 with incomplete root formation. The Signs statistical test was used to evaluate the comparison between loss and contralateral hemiarches. Results: In 20 (37%) of 54 subjects, the L8 was better positioned in the hemiarch with loss of the lower first molar (p<0.001) compared with the control side. In the remaining 34 subjects, no difference was found. When only the L8 considered as impacted on the control side was examined (n=30), the cases with better positioning on the side with L6 loss increased to 66.6% (p<0.001). Conclusion: The loss of lower first molars improves the position of the lower third molar during its active eruption, mainly when the lower third molar is impacted. However, L6 loss does not affect the root development of lower third molars