Genome-wide association study identifies novel loci associated with circulating phospho- and sphingolipid concentrations

Phospho- and sphingolipids are crucial cellular and intracellular compounds. These lipids are required for active transport, a number of enzymatic processes, membrane formation, and cell signalling. Disruption of their metabolism leads to several diseases, with diverse neurological, psychiatric, and metabolic consequences. A large number of phospholipid and sphingolipid species can be detected and measured in human plasma. We conducted a meta-analysis of five European family-based genome-wide association studies (N = 4034) on plasma levels of 24 sphingomyelins (SPM), 9 ceramides (CER), 57 phosphatidylcholines (PC), 20 lysophosphatidylcholines (LPC), 27 phosphatidylethanolamines (PE), and 16 PE-based plasmalogens (PLPE), as well as their proportions in each major class. This effort yielded 25 genome-wide significant loci for phospholipids (smallest P-value = 9.88×10⁻²⁰⁴) and 10 loci for sphingolipids (smallest P-value = 3.10×10⁻⁵⁷). After a correction for multiple comparisons (P-value<2.2×10⁻⁹), we observed four novel loci significantly associated with phospholipids (PAQR9, AGPAT1, PKD2L1, PDXDC1) and two with sphingolipids (PLD2 and APOE) explaining up to 3.1% of the variance. Further analysis of the top findings with respect to within class molar proportions uncovered three additional loci for phospholipids (PNLIPRP2, PCDH20, and ABDH3) suggesting their involvement in either fatty acid elongation/saturation processes or fatty acid specific turnover mechanisms. Among those, 14 loci (KCNH7, AGPAT1, PNLIPRP2, SYT9, FADS1-2-3, DLG2, APOA1, ELOVL2, CDK17, LIPC, PDXDC1, PLD2, LASS4, and APOE) mapped into the glycerophospholipid and 12 loci (ILKAP, ITGA9, AGPAT1, FADS1-2-3, APOA1, PCDH20, LIPC, PDXDC1, SGPP1, APOE, LASS4, and PLD2) to the sphingolipid pathways. In large meta-analyses, associations between FADS1-2-3 and carotid intima media thickness, AGPAT1 and type 2 diabetes, and APOA1 and coronary artery disease were observed. In conclusion, our study identified nine novel phospho- and sphingolipid loci, substantially increasing our knowledge of the genetic basis for these traits.     

Coumarin glucosides from Cruciata taurica

Two new coumarin glycosides (1 and 2) along with two known coumarin glucosides, daphnin (3) and daphnetin glucoside (4) were isolated from the aerial parts of Cruciata taurica. The structures of the new compounds were elucidated by spectral methods and chemical means as 7-O-(6' -acetoxy-beta-D-glucopyranosyl)-8-hydroxycoumarin (1) and 7-O-[6 '-O-(3',4'-dihydroxycinnamoyl)-beta-D-glucopyranosyl]-8-hydroxycoumarin (2). The phylogenetic significance of coumarins in C. taurica was discussed.     

A new therapeutic approach in Alzheimer disease: some novel pyrazole derivatives as dual MAO-B inhibitors and antiinflammatory analgesics

The increasing life expectancy in our population makes Alzheimer's disease (AD) a growing public health problem. There is a great need to find a way to prevent and delay the disease. It was shown that monoamine oxidase-B (MAO-B) inhibitors and antiinflammatory agents might be effective in treating AD. Therefore, a novel series of 1-thiocarbamoyl-3-substituted phenyl-5-(2-pyrrolyl)-4,5-dihydro-(1H)-pyrazole derivatives as promising MAO-B inhibitors was synthesized and investigated for the ability to inhibit selectively the activity of the A and B isoforms of monoamine oxidase (MAO). Most of the synthesized compounds showed high activity against both the MAO-A (compounds 3e-3h) and the MAO-B (compounds 3i-3l) isoforms. All the synthesized compounds were also tested for their in vivo antiinflammatory activity by two different bioassays namely, carrageenan-induced oedema and acetic acid-induced increase in capillary permeability in mice. In addition, analgesic and ulcerogenic activities were determined. The combined antiinflammatory data from in vivo animal models showed that compound 3k exhibited anti-inflammatory activity comparable to that of indomethacin with no ulcerogenic effects. Since compound 3k exhibits both antiinflammatory-analgesic activity and MAO-B inhibition, it needs further detailed studies.     

Bacterial extract cantastim activates macrophages via TLR-2

CANTASTIM is a second generation bacterial immunomodulator. The aim of this study was to examine the mechanism by which bacterial immunomodulator CANTASTIM induces production of inflammatory cytokines in monocytes/macrophages. Proinflammatory cytokines were induced in PMA-differentiated THP-1 cells by stimulation with TLR agonists and CANTASTIM in the presence or absence of anti-TLR blocking antibodies or isotype matched control antibodies. Also, RNA interference was used to knockdown TLR2 or TLR4 expression in PMA-differentiated THP-1 cells before stimulation. As expected, induction of TNF-alpha and IL-6 by TLR4 agonist LPS was inhibited in a significant manner by anti-TLR4 but not by anti-TLR2 antibody. Unexpectedly, treatment with anti-LR2 blocking antibody inhibited only IL-6 production induced by Pam3CSK4 while the level of TNF-alpha was unchanged. When cells were stimulated by TLR2 agonist heat-killed Listeria monocytogenes the release of TNF-alpha was significantly attenuated by anti-TLR2 antibodies. Silencing of TLR2 led to a statistically significant inhibition of TNF-alpha secretion induced by TLR2 agonist while siRNA silencing of TLR4 did not affect the response to TLR2 agonist. Cells exposed to CANTASTIM produced significant levels of pro-inflammatory cytokines but the levels were lower than LPS-stimulated cells. Production of both cytokines was inhibited by treatment with anti-TLR2 blocking antibody and not by anti-TLR4 antibody. Silencing of TLR2 led to a statistically significant inhibition of TNF-a secretion induced by CANTASTIM while silencing of TLR4 had no effect on the response to CANTASTIM. These results support the hypothesis that CANTASTIM may exert its immunomodulatory and adjuvant activities through interaction of its bacterial components with TLR2.     

Cytotoxic and genotoxic effects of <Emphasis Type="Italic">Lavandula stoechas</Emphasis> aqueous extracts

Lavandula genus is an important member of Labiatae (Lamiaceae) family. People use commonly Lavandula stoechas as a medicinal plant for various diseases around the world and also in Turkey. The aim of this study was to investigate cytotoxic and genotoxic effects of aqueous extracts (40, 80 and 120 g/L) from L. stoechas flowers on Allium cepa root tip meristem cells. For this purpose, A. cepa onion bulbs were treated with the above-mentioned L. stoechas flower extracts for 72 h. Spring water (pH 7.3) was used as a control. The result of this study sowed that aqueous extracts reduced mitotic index, but induced chromosome aberrations and mitotic aberrations in comparison with control, significantly (p < 0.05). Aqueous extracts induced breaks, stickiness, pole deviations and micronuclei. Furthermore, these effects were related to extract concentrations. These results showed that L. stoechas aqueous extracts have cytotoxic and genotoxic effects.     

Polyaniline grafted polyacylonitrile conductive composite fibers for reversible immobilization of enzymes: Stability and catalytic properties of invertase

Polyacylonitrile fibers (PAN) surfaces were modified with chemical polymerization of conductive polyaniline (PANI) in the presence of potassium dichromate as an oxidizing agent. The effect of aniline concentration on the grafting efficiency and on the electrical surface resistance of PAN/PANI composite fibers was investigated. The surface resistance of the conductive composite fibers in this work was found to be between 8.0 and 0.5 kΩ/cm. As the amount of grafted PANI increased on the PAN fibers the electrical resistance of composite fibers decreased. The PAN/PANI composite fibers were characterized by SEM and FTIR studies. Composite PAN/PANI fibers were used for reversible immobilization of invertase. The immobilization efficiency and the activity of the immobilized invertase (from 1.0 mg/mL invertase solution at pH 5.5) were increased with increasing PANI contents of the composite fibers. The maximum amount of immobilized enzyme onto composite fibers containing 2.0% PANI was about 76.6 mg/g. The optimum pH for the free enzyme was observed at 5.0. On the other hand, immobilized invertase yielded a broad optimum pH profile between pH 5.0 and 7.0. Immobilized invertase exhibited 83% of its original activity even after two months storage at 4 °C while the free enzyme showed only 7% of its initial activity.     

Two new species of the genus <Emphasis Type="Italic">Quadroppia</Emphasis> (Acari: Oribatida: Quadroppiidae) from Turkey

Two new species of the genus Quadroppia Jacot, 1939, Quadroppia (Coronoquadroppia) squarrosa sp. n. and Quadroppia (Quadroppia) foveolata sp. n. are described and illustrated from Turkey. They were collected from soil and litter under pear trees (Pyrus communis) and moss on rock, respectively.     

Plants used as natural dye sources in Turkey

This study was carried out in the regions where handcrafts such as carpet and rug weaving are common in Turkey. In the regions where natural dyes are used, 123 plant species belonging to 50 families were identified as sources of natural dyes. In natural dye production, different parts of the plant or the whole aboveground plant is used. Ten different colors are gained from the plants. Sometimes the same color can be obtained from different plants. By mixing different plants, it is possible to produce various colors. We also identified more than 12 natural and more than eight chemical assistant substances (mordant) that are used in the regions to bind dye to fibers, to maintain the strongness and brightness of the colors, and to obtain various colors     

New taxa described in Zoology in the Middle East

Abstract

The region between Mersin and ?skenderun was selected for studying marine turtles in the Turkish waters of the Mediterranean sea, as the most important nesting grounds of Green Turtles (Chelonia mydas) in the Mediterranean are situated there. In the 1995–96 fishing season, the 5 trawl boats taking part in the project reported that nets in the Eastern Mediterranean trapped 160 Green Turtles and 26 Loggerhead Turtles (Caretta caretta). In the following trawling season (1996/97), 306 Green Turtles, 116 Loggerhead Turtles (Caretta caretta) and 437 Nile Soft-shelled Turtles (Trionyx triunguis) were found to be trapped as a by-catch in the trawling nets. 87% of these turtles were captured by mid-trawling nets, the rest by bottom-trawling nets, mostly at depths of 11–30 m. 95% of all turtles were caught alive and healthy, and were usually released back into the sea immediately after capture by the fishermen. Training measures were given to local fishermen in order to raise their awareness of the threats to marine turtles.