Common promoter variant in cyclooxygenase-2 represses gene expression: evidence of role in acute-phase inflammatory response

Objective: Cyclooxygenase (COX)-2 is a key regulatory enzyme in the synthesis of prostanoids associated with trauma and inflammation. We investigated the COX-2 gene for functional variants that may influence susceptibility to disease. Methods and results: The promoter of COX-2 was screened for variants in healthy subjects by use of polymerase chain reaction-based methods. Promoter activity was investigated by using reporter expression experiments in human lung fibroblasts. Patients undergoing coronary artery bypass graft surgery, with measurements of plasma markers linked to COX-2 activity, were genotyped for association studies. A common COX-2 promoter variant, -765G>C, was found and shown to be carried by >25% of a group of healthy UK subjects. The -765C allele had significantly lower promoter activity compared with -765G, basally (28±3% lower, P<0.005) and in serum-stimulated cells (31±2% lower, P<0.005). In patients subjected to coronary artery bypass graft surgery, the magnitude of rise in levels of C-reactive protein (CRP) was strongly genotype dependent. Compared with -765G homozygotes, patients carrying the -765C allele had significantly lower plasma CRP levels at 1 to 4 days after surgery (14% lower at the peak of CRP levels on day 3, P<0.05 for all time points). Conclusions: For several acute and chronic inflammatory diseases, -765G>C may influence the variability of response observed

A programmable, multi-format photonic transceiver platform enabling flexible optical networks

Development of programmable photonic devices for future flexible optical networks is ongoing. To this end, an innovative, multi-format QAM transmitter design is presented. It comprises a segmented-electrode InP IQ-MZM to be fabricated in InP, which can be directly driven by low-power CMOS logic. Arbitrary optical QAM format generation is made possible using only binary electrical signals, without the need for high-performance DACs and high-swing linear drivers. The concept enables a host of Tx-side DSP functionality, including the spectral shaping needed for Nyquist-WDM system concepts. In addition, we report on the development of an optical channel MUX/DEMUX, based on arrays of microresonator filters with reconfigurable bandwidths and center wavelengths. The device is intended for operation with multi-format flexible transceivers, enabling Dense (D)WDM superchannel aggregation and arbitrary spectral slicing in the context of a flexible grid environment

Design principles for the future internet architecture

Design principles play a central role in the architecture of the Internet as driving most engineering decisions at conception level and operational level. This paper is based on the EC Future Internet Architecture (FIArch) Group results and identifies some of the design principles that we expect to govern the future architecture of the Internet. We believe that it may serve as a starting point and comparison for most research and development projects that target the so-called Future Internet Architecture

Current evidence for a modulation of low back pain by human genetic variants

The manifestation of chronic back pain depends on structural, psychosocial, occupational and genetic influences. Heritability estimates for back pain range from 30% to 45%. Genetic influences are caused by genes affecting intervertebral disc degeneration or the immune response and genes involved in pain perception, signalling and psychological processing. This inter-individual variability which is partly due to genetic differences would require an individualized pain management to prevent the transition from acute to chronic back pain or improve the outcome. The genetic profile may help to define patients at high risk for chronic pain. We summarize genetic factors that (i) impact on intervertebral disc stability, namely Collagen IX, COL9A3, COL11A1, COL11A2, COL1A1, aggrecan (AGAN), cartilage intermediate layer protein, vitamin D receptor, metalloproteinsase-3 (MMP3), MMP9, and thrombospondin-2, (ii) modify inflammation, namely interleukin-1 (IL-1) locus genes and IL-6 and (iii) and pain signalling namely guanine triphosphate (GTP) cyclohydrolase 1, catechol-O-methyltransferase, μ opioid receptor (OPMR1), melanocortin 1 receptor (MC1R), transient receptor potential channel A1 and fatty acid amide hydrolase and analgesic drug metabolism (cytochrome P450 [CYP]2D6, CYP2C9)

Association between COX-2 rs 6681231 Genotype and Interleukin-6 in Periodontal Connective Tissue. A Pilot Study

This study was partially undertaken at the UCL Eastman Dental Institute, which received a proportion of funding from the Department of Health’s National Institute of Health Research (NIHR) Biomedical Research Centres funding scheme