Human genetic selection on the MTHFR 677C>T polymorphism

<p>Abstract</p> <p>Background</p> <p>The prevalence of genotypes of the 677C>T polymorphism for the MTHFR gene varies among humans. In previous studies, we found changes in the genotypic frequencies of this polymorphism in populations of different ages, suggesting that this could be caused by an increase in the intake of folate and multivitamins by women during the periconceptional period. The aim was to analyze changes in the allelic frequencies of this polymorphism in a Spanish population, including samples from spontaneous abortions (SA).</p> <p>Methods</p> <p>A total of 1305 subjects born in the 20th century were genotyped for the 677C>T polymorphism using allele specific real-time PCR with Taqman^®probes. A section of our population (n = 276) born in 1980–1989 was compared with fetal samples (n = 344) from SA of unknown etiology from the same period.</p> <p>Results</p> <p>An increase in the frequency of the T allele (0.38 vs 0.47; p < 0.001) and of the TT genotype (0.14 vs 0.24; p < 0.001) in subjects born in the last quarter of the century was observed. In the 1980–1989 period, the results show that the frequency of the wild type genotype (CC) is about tenfold lower in the SA samples than in the controls (0.03 vs 0.33; p < 0.001) and that the frequency of the TT genotype increases in the controls (0.19 to 0.27) and in the SA samples (0.20 to 0.33 (p < 0.01)); r = 0.98.</p> <p>Conclusion</p> <p>Selection in favor of the T allele has been detected. This selection could be due to the increased fetal viability in early stages of embryonic development, as is deduced by the increase of mutants in both living and SA populations.</p

Fermented wheat germ extract - nutritional supplement or anticancer drug?

<p>Abstract</p> <p>Background</p> <p>Fermented wheat germ extract (FWGE) is a multisubstance composition and, besides others, contains 2-methoxy benzoquinone and 2, 6-dimethoxy benzoquinone which are likely to exert some of its biological effects. FWGE interferes with anaerobic glycolysis, pentose cycle and ribonucleotide reductase. It has significant antiproliferative effects and kills tumor cells by the induction of apoptosis via the caspase-poly [ADP-ribose] polymerase-pathway. FWGE interacts synergistically with a variety of different anticancer drugs and exerted antimetastatic properties in mouse models. In addition, FWGE modulates immune response by downregulation of MHC-I complex and the induction of TNF-α and various interleukins. Data in the F-344 rat model provide evidence for a colon cancer preventing effect of FWGE.</p> <p>Clinical data from a randomized phase II trial in melanoma patients indicate a significant benefit for patients treated with dacarbazine in combination with FWGE in terms of progression free survival (PFS) and overall survival (OS). Similarly, data from studies in colorectal cancer suggested a benefit of FWGE treatment. Besides extension of OS and PFS, FWGE improved the quality of life in several studies.</p> <p>Conclusion</p> <p>In conclusion, available data so far, justify the use of FWGE as a non-prescription medical nutriment for cancer patients. Further randomized, controlled and large scale clinical studies are mandatory, to further clarify the value of FWGE as a drug component of future chemotherapy regimens.</p

An hp -adaptive discontinuous Galerkin method for modelling snap loads in mooring cables

This paper focuses on modelling snap loads in mooring cables. Snap loads are a known problem for the established oil and gas industry, and they pose a major challenge to robust mooring design for the growing industry of wave energy conversion. We present a discontinuous Galerkin formulation using a local Lax-Friedrich Riemann solver to capture snap loads in mooring cables with high accuracy. An hp−adaptive scheme is used to dynamically change the mesh size h and the polynomial order p, based on the local solution quality. We implement an error indicator and a shock identifier to capture shocks with slope-limited linear elements, while using high-order Legendre polynomials for smooth solution regions. The results show exponential error convergence of order p + 1∕2 for smooth solutions. Efficient and accurate computations of idealised shock waves in both linear and nonlinear materials were achieved using hp−adaptivity. Comparison with experimental data gives excellent results, including snap load propagation in a mooring chain. Application on a wave energy device using coupled simulations highlights the importance of the touch-down region in catenary moorings. We conclude that the formulation is able to handle snap loads with good accuracy, with implications for both maximum peak load and fatigue load estimates of mooring cables