Identification of a novel FGFRL1 MicroRNA target site polymorphism for bone mineral density in meta-analyses of genome-wide association studies

MicroRNAs (miRNAs) are critical post-transcriptional regulators. Based on a previous genome-wide association (GWA) scan, we conducted a polymorphism in microRNAs' Target Sites (poly-miRTS)-centric multistage meta-analysis for lumbar spine (LS)-, total hip (HIP)-, and femoral neck (FN)-bone mineral density (BMD). In stage I, 41,102 poly-miRTSs were meta-analyzed in 7 cohorts with a genome-wide significance (GWS) α=0.05/41,102=1.22×10-6. By applying α=5×10-5 (suggestive significance), 11 poly-miRTSs were selected, with FGFRL1 rs4647940 and PRR5 rs3213550 as top signals for FN-BMD (P-value=7.67×10-6 and 1.58×10-5) in gender-combined sample. In stage II in silico replication (two cohorts), FGFRL1 rs4647940 was the only signal marginally replicated for FN-BMD (P-value=5.08×10-3) at α=0.10/11=9.09×10-3. PRR5 rs3213550 was also selected based on biological significance. In stage III de novo genotyping replication (two cohorts), FGFRL1 rs4647940 was the only signal significantly replicated for FN-BMD (P-value=7.55×10-6) at α=0.05/2=0.025 in gender-combined sample. Aggregating three stages, FGFRL1 rs4647940 was the single stage I-discovered and stages II- and III-replicated signal attaining GWS for FN-BMD (P-value=8.87×10-12). Dual-luciferase reporter assays demonstrated that FGFRL1 3' untranslated region harboring rs4647940 appears to be hsa-miR-140-5p's target site. In a zebrafish microinjection experiment, dre-miR-140-5p is shown to exert a dramatic impact on craniofacial skeleton formation. Taken together, we provided functional evidence for a novel FGFRL1 poly-miRTS rs4647940 in a previously known 4p16.3 locus, and experimental and clinical genetics studies have shown both FGFRL1 and hsa-miR-140-5p are important for bone formation. © The Author 2015. Published by Oxford University Press. All rights reserved.

Studies on boundary lubrication properties of oxidised coconut and soy bean oils

Vegetable oils are a potential source of base oils for biodegradable lubricants, with limited oxidative stability. This study focuses on the effect of long-term ageing and the influence of oxidation products on the boundary lubrication performance of coconut and soy bean oils, by subjecting them to accelerated ageing in a dark oven at elevated temperature. The samples were collected at regular intervals and analysed for the changes in viscosity, percentage of free fatty acid and peroxide number compared to fresh oil samples. The boundary lubrication properties of these samples were evaluated using a four-ball tester. Increased wear observed with aged oil samples was linked to the destruction of triglyceride structure and formation of peroxides. The difference in the wear properties of soy bean oil to coconut oil was accounted by its high content of unsaturated fatty acids and its susceptibility to undergo oxidation. It was concluded that the coconut oil can perform as a better lubricant and has got a better storage life compared to soy bean oil.

Titration calorimetric studies to elucidate the specificity of the interactions of polymyxin B with lipopolysaccharides and lipid A

Lipopolysaccharide (LPS), the major cell wall constituent of Gram-negative bacteria, evokes a multitude of biological effects in mammals including pyrogenicity and toxic shock syndrome. Polymyxin B (PmB), a polycationic cyclic peptide, is known to neutralize most of its activities. The nature of the interaction of PmB with LPS and lipid A was investigated by isothermal titration calorimetry. PmB binds to LPS as well as lipid A stoichiometrically and non-co-operatively with micromolar affinity. These interactions are driven primarily by a favourable change in entropy (delta S) and are endothermic in nature. These positive changes in enthalpies decrease with increasing temperature, yielding a heat capacity change, delta Cp, of -2385 J.mol-1.degree-1 for PmB-LPS interactions while the binding of PmB to lipid A displays a delta Cp of -2259 J.mol-1.degree-1. The negative heat capacity changes provide strong evidence for the role of hydrophobic interactions as the driving force for the association of PmB with LPS and lipid A. A correlation of the energetics of these interactions with analyses of the molecular models of PmB suggests that a cluster of solvent-exposed non-polar amino acid side-chains that line one surface of the molecule, together with a ring of positively charged residues on its other surface, are responsible for its strong and stoichiometric binding to LPS.

Spin-Probe ESR Studies on Nanocomposite Polymer Electrolytes

The possibility of using spin-probe electron spin resonance (ESR) as a tool to study glass transition temperature, T g, of polymer electrolytes is explored in 4 hydroxy 2,2,6,6 tetramethylpiperidine N oxyl (TEMPOL) doped composite polymer electrolyte (PEG)46LiClO4 dispersed with nanoparticles of hydrotalcite. The T g is estimated from the measured values of T 50G, the temperature at which the extrema separation 2A zz of the broad powder spectrum decreases to 50 G. In another method, the correlation time τc for the spin probe dynamics was determined by computer simulation of the ESR spectra and T g has been identified as the temperature at which τc begins to show temperature dependence. While both methods give values of T g close to those obtained from differential scanning calorimetry, it is concluded that more work is required to establish spin-probe ESR as a reliable technique for the determination of T g.