Plasma Homocysteine Is Not Subject to Seasonal Variation.

Background: Studies investigating the relationship between plasma total homocysteine (tHcy) and vascular disease usually rely on a single measurement. Little information is available, however, on the seasonal variability of plasma tHcy. The aim of this study was to investigate the seasonal variation in fasting plasma tHcy and related B-vitamin intake and status in a group of people who did not consume fortified foods or take B-vitamin supplements. Methods: In this longitudinal study, a group of 22 healthy people were followed for 1 year. A fasting blood sample and dietary information were collected from each individual every 3 months, i.e., at the end of each season. Results: There was no significant seasonal variation in plasma tHcy or in B-vitamin intake or status with the exception of red cell folate (significantly lower in spring compared with autumn or winter) and serum folate (significantly lower in spring compared with the other seasons). Although the between-person variation in plasma tHcy was high (47%), the within-person variation was low (11%). This low variation, combined with the low methodologic imprecision of 3.8%, yielded a high reliability coefficient for plasma tHcy (0.97). Conclusions: Although there was a small seasonal variation in folate status, there was no corresponding seasonal variation in plasma tHcy. The high reliability coefficient for plasma tHcy suggests that a single measurement is reflective of an individual’s average plasma tHcy concentration, thus indicating its usefulness as a potential predictor of disease. This, however, needs to be confirmed in different subgroups of the population.

Analysis of receptor (CD46, CD150) usage by measles virus

This is a collaborative paper between Juergen Schneider-Schaulies's group and ours. It shows the differential use of the two measles receptors in various strains.

On the brightness distribution of type ia supernovae from violent white dwarf mergers

We investigate the brightness distribution expected for thermonuclear explosions that might result from the ignition of a detonation during the violent merger of white dwarf (WD) binaries. Violent WD mergers are a subclass of the canonical double degenerate scenario where two carbon-oxygen (CO) WDs merge when the larger WD fills its Roche lobe. Determining their brightness distribution is critical for evaluating whether such an explosion model could be responsible for a significant fraction of the observed population of Type Ia supernovae (SNe Ia). We argue that the brightness of an explosion realized via the violent merger model is mainly determined by the mass of Ni produced in the detonation of the primary COWD. To quantify this link, we use a set of sub-Chandrasekhar mass WD detonation models to derive a relationship between primary WD mass (m) and expected peak bolometric brightness (M). We use this m-M relationship to convert the masses of merging primary WDs from binary population models to a predicted distribution of explosion brightness. We also investigate the sensitivity of our results to assumptions about the conditions required to realize a detonation during violent mergers ofWDs. We find a striking similarity between the shape of our theoretical peak-magnitude distribution and that observed for SNe Ia: our model produces a M distribution that roughly covers the range and matches the shape of the one observed for SNe Ia. However, this agreement hinges on a particular phase of mass accretion during binary evolution: the primary WD gains ~0.15-0.35M? from a slightly evolved helium star companion. In our standard binary evolution model, such an accretion phase is predicted to occur for about 43 per cent of all binary systems that ultimately give rise to binary CO WD mergers. We also find that with high probability, violent WD mergers involving the most massive primaries (?1.3M?, which should produce bright SNe) have delay times ?500 Myr. © 2012 The Authors. Published by Oxford University Press on behalf of the Royal Astronomical Society.

Analysis of Histone Deacetylase 7 (HDAC7) Alternative Splicing and Its Role in Embryonic Stem Cell Differentiation Toward Smooth Muscle Lineage

Histone deacetylases (HDACs) have a central role in the regulation of gene expression, which undergoes alternative splicing during embryonic stem cell (ES) cell differentiation. Alternative splicing gives rise to vast diversity over gene information, arousing public concerns in the last decade. In this chapter, we describe a strategy to detect HDAC7 alternative splicing and analyze its function on ES cell differentiation.

RAS mutations and cetuximab in locally advanced rectal cancer: results of the EXPERT-C trial.

Background: RAS mutations predict resistance to anti-epidermal growthfactor receptor (EGFR) monoclonal antibodies in metastatic colorectal cancer. We analysed RAS mutations in 30 non-metastatic rectal cancer patients treated with or without cetuximab within the 31 EXPERT-C trial.

Methods: Ninety of 149 patients with tumours available for analysis were KRAS/BRAF wild-type, and randomly assigned to capecitabine plus oxaliplatin (CAPOX) followed by chemoradiotherapy, surgery and adjuvant CAPOX or the same regimen plus cetuximab (CAPOX-C). Of these, four had a mutation of NRAS exon 3, and 84 were retrospectively analysed for additional KRAS (exon 4) and NRAS (exons 2/4) mutations by using bi-directional Sanger sequencing. The effect of cetuximab on study end-points in the RAS wild-type population was analysed.

Results: Eleven (13%) of 84 patients initially classified as KRAS/BRAF wild-type were found to have a mutation in KRAS exon 4 (11%) or NRAS exons 2/4 (2%). Overall, 78/149 (52%) assessable patients were RAS wild-type (CAPOX, n = 40; CAPOX-C, n = 38). In this population, after a median follow-up of 63.8 months, in line with the initial analysis, the addition of cetuximab was associated with numerically higher, but not statistically significant, rates of complete response (15.8% versus 7.5%, p = 0.31), 5-year progression-free survival (75.5% versus 67.5%, hazard ratio (HR) 0.61, p = 0.25) and 5-year overall survival (83.8% versus 70%, HR 0.54, p = 0.20).

Conclusions: RAS mutations beyond KRAS exon 2 and 3 were identified in 17% of locally advanced rectal cancer patients. Given the small sample size, no definitive conclusions on the effect of additional RAS mutations on cetuximab treatment in this setting can be drawn and further investigation of RAS in larger studies is warranted.