PGRMC1 phosphorylation affects cell shape, motility, glycolysis, mitochondrial form and function, and tumor growth.

BackgroundProgesterone Receptor Membrane Component 1 (PGRMC1) is expressed in many cancer cells, where it is associated with detrimental patient outcomes. It contains phosphorylated tyrosines which evolutionarily preceded deuterostome gastrulation and tissue differentiation mechanisms.ResultsWe demonstrate that manipulating PGRMC1 phosphorylation status in MIA PaCa-2 (MP) cells imposes broad pleiotropic effects. Relative to parental cells over-expressing hemagglutinin-tagged wild-type (WT) PGRMC1-HA, cells expressing a PGRMC1-HA-S57A/S181A double mutant (DM) exhibited reduced levels of proteins involved in energy metabolism and mitochondrial function, and altered glucose metabolism suggesting modulation of the Warburg effect. This was associated with increased PI3K/AKT activity, altered cell shape, actin cytoskeleton, motility, and mitochondrial properties. An S57A/Y180F/S181A triple mutant (TM) indicated the involvement of Y180 in PI3K/AKT activation. Mutation of Y180F strongly attenuated subcutaneous xenograft tumor growth in NOD-SCID gamma mice. Elsewhere we demonstrate altered metabolism, mutation incidence, and epigenetic status in these cells.ConclusionsAltogether, these results indicate that mutational manipulation of PGRMC1 phosphorylation status exerts broad pleiotropic effects relevant to cancer and other cell biology

Sucrose in the concentrated solution or the supercooled “state” : a review of caramelisation reactions and physical behaviour

Sucrose is probably one of the most studied molecules by food scientists, since it plays an important role as an ingredient or preserving agent in many formulations and technological processes. When sucrose is present in a product with a concentration near or greater than the saturation point—i.e. in the supercooled state—it possesses high potentialities for the food industry in areas as different as pastry industry, dairy and frozen desserts or films and coatings production. This paper presents a review on critical issues and research on highly concentrated sucrose solutions—mainly, on sucrose thermal degradation and relaxation behaviour in such solutions. The reviewed works allow identifying several issues with great potential for contributing to significant advances in Food Science and Technology.Authors are grateful for the valuable discussions with Teresa S. Brandao and Rosiane Lopes da Cunha during this research. Author M. A. C. Quintas acknowledges the financial support of her research by FCT grant SFRH/BPD/41715/2007

Mean DNA bend angle and distribution of DNA bend angles in the CAP-DNA complex in solution.

In order to define the mean DNA bend angle and distribution of DNA bend angles in the catabolite activator protein (CAP)-DNA complex in solution under standard transcription initiation conditions, we have performed nanosecond time-resolved fluorescence measurements quantifying energy transfer between a probe incorporated at a specific site in CAP, and a complementary probe incorporated at each of five specific sites in DNA. The results indicate that the mean DNA bend angle is 77(+/-3) degrees - consistent with the mean DNA bend angle observed in crystallographic structures (80(+/-12) degrees ). Lifetime-distribution analysis indicates that the distribution of DNA bend angles is relatively narrow, with <10 % of DNA bend angles exceeding 100 degrees. Millisecond time-resolved luminescence measurements using lanthanide-chelate probes provide independent evidence that the upper limit of the distribution of DNA bend angles is approximately 100 degrees. The methods used here will permit mutational analysis of CAP-induced DNA bending and the role of CAP-induced DNA bending in transcriptional activation

Leg skinfold thicknesses and race performance in male 24-hour ultra-marathoners

The association of skinfold thicknesses with race performance has been investigated in runners competing over distances of ≤50 km. This study investigated a potential relation between skinfold thicknesses and race performance in male ultra-marathoners completing >50 km in 24 hours. Variables of anthropometry, training, and previous performance were related to race performance in 63 male ultra-marathoners aged 46.9 (standard deviation [SD] 10.3) years, standing 1.78 (SD 0.07) m in height, and weighing 73.3 (SD 7.6) kg. The runners clocked 146.1 (SD 43.1) km during the 24 hours. In the bivariate analysis, several variables were associated with race performance: body mass (r = -0.25); skinfold thickness at axilla (r = -0.37), subscapula (r = -0.28), abdomen (r = -0.31), and suprailiaca (r = -0.30); the sum of skinfold thicknesses (r = -0.32); percentage body fat (r = -0.32); weekly kilometers run (r = 0.31); personal best time in a marathon (r = -0.58); personal best time in a 100-km ultra-run (r = -0.31); and personal best performance in a 24-hour run (r = 0.46). In the multivariate analysis, no anthropometric or training variable was related to race performance. In conclusion, in contrast to runners up to distances of 50 km, skinfold thicknesses of the lower limbs were not related to race performance in 24-hour ultra-marathoners