Hepatic VLDL secretion : DGAT1 determines particle size but not particle number, which can be supported entirely by DGAT2

We investigated whether, in view of its activity being expressed on both aspects of the endoplasmic reticulum (ER; dual membrane topology), diacylglycerol acyltransferase 1 (DGAT1) plays a distinctive role in determining the triglyceride (TAG) content of VLDL particles secreted by the liver. Mice in which the DGAT1 gene was specifically ablated in hepatocytes (DGAT1-LKO mice) had the same number of VLDL particles (apoB concentration) in the plasma 1 h after Triton 1339 treatment, but these particles were approximately half the size of VLDL particles secreted by control mice and had a proportionately decreased content of TAG, with normal cholesterol and cholesteryl ester contents. Analyses of purified microsomal fractions prepared from 16 h fasted control and DAGT1-LKO mice showed that the TAG/protein ratio in the ER was significantly lower in the latter. Electron micrographs of these livers showed that those from DGAT1-LKO mice did not show the increased lipid content of the smooth ER shown by control livers. The effects of DGAT1- and DGAT2-specific inhibitors on apoB secretion by HepG2 cells showed that DGAT1 is not indispensable for apoB secretion and demonstrated redundancy in the ability of the two enzymes to support apoB secretion. Therefore, our findings show that DGAT1 is essential for the complete lipidation and maturation of VLDL particles within the lumen of the ER, consistent with its dual topology within the ER membrane. In the mouse, DGAT2 can support apoB secretion (particle number) even when TAG availability for full VLDL lipidation is restricted in the absence of DGAT1

Warm temperature acclimation impacts metabolism of paralytic shellfish toxins from Alexandrium minutum in commercial oysters

© 2015 John Wiley & Sons Ltd. Species of Alexandrium produce potent neurotoxins termed paralytic shellfish toxins and are expanding their ranges worldwide, concurrent with increases in sea surface temperature. The metabolism of molluscs is temperature dependent, and increases in ocean temperature may influence both the abundance and distribution of Alexandrium and the dynamics of toxin uptake and depuration in shellfish. Here, we conducted a large-scale study of the effect of temperature on the uptake and depuration of paralytic shellfish toxins in three commercial oysters (Saccostrea glomerata and diploid and triploid Crassostrea gigas, n = 252 per species/ploidy level). Oysters were acclimated to two constant temperatures, reflecting current and predicted climate scenarios (22 and 27 °C), and fed a diet including the paralytic shellfish toxin-producing species Alexandrium minutum. While the oysters fed on A. minutum in similar quantities, concentrations of the toxin analogue GTX1,4 were significantly lower in warm-acclimated S. glomerata and diploid C. gigas after 12 days. Following exposure to A. minutum, toxicity of triploid C. gigas was not affected by temperature. Generally, detoxification rates were reduced in warm-acclimated oysters. The routine metabolism of the oysters was not affected by the toxins, but a significant effect was found at a cellular level in diploid C. gigas. The increasing incidences of Alexandrium blooms worldwide are a challenge for shellfish food safety regulation. Our findings indicate that rising ocean temperatures may reduce paralytic shellfish toxin accumulation in two of the three oyster types; however, they may persist for longer periods in oyster tissue

Breaking bad news in cancer : an assessment of Maltese patients’ preferences

Purpose: It is unclear whether Maltese cancer patients wish to know their diagnosis or to what extent they want to be informed. The aim was to assess patients’ preferences for receiving a cancer diagnosis and being involved in the decision-making process, and then compare these with results from similar international studies. Methods: Two hundred fifty-two Maltese adult cancer patients were invited to complete two standardised tools: the Measure of Patients’ Perspective (MPP), assessing patients’ preferences for receiving news about their cancer, and the Control Preferences Scale (CPS), examining involvement in decision-making. Results: Maltese patients rated the ‘content’ subscale (information given; mean 4.17, SD 0.59) as significantly more important (p<0.001) than ‘support’ (offering comfort/support; mean 3.73, SD 0.68) and ‘facilitation’ (how information is given; mean 3.86, SD 0.68). Patients with higher levels of education had significantly higher scores for ‘content’ (p=0.018) and ‘facilitation’ (p<0.001) on the MPP, while lower education levels preferred a passive role (p=0.01) on the CPS. Although there is a trend towards a collaborative and even an active role in treatment decisions, patients still exhibit a paternalistic attitude towards their physician. Age, gender and medical variables had no significant influence on response. Conclusions: Maltese cancer patients want to be informed of their cancer diagnosis, its treatment and prognosis, similar to other international studies. However, 60% of Maltese patients prefer a more paternalistic approach towards their physician when compared to other studies.peer-reviewe