Analysis of changes in triacylglycerol ratios in mouse liver and plasma in response to a liver X receptor agonist

An LC-MS method was developed for the analysis of triacylglycerols (TAG) in mouse liver extracts and plasma samples. C57 Mice were treated with two LXR agonists that have been shown to upregulate TAGs, T0901317 (T1317) or Org 264693 and compared to vehicle dosed animals. The dose used was 30 mg kg⁻¹, once daily, with three different dose regimes; 24 H, 48 H and 5 day. The TAG ratios measured were C52:2/C54:3 and C52:3/C54:4, which corresponded to a decrease in the palmitate and an increase in oleate composition of the TAGs. A significant change in the C52:2/C54:3 ratio was observed with all dose regimes and a good correlation was obtained between liver and plasma samples. In a separate study, the same compounds were dosed to LXR α and LXR β knock-out (KO) mice at 30 mg kg⁻¹, once daily, for 5 days. The LXR β KO mice showed similar TAG ratio changes to the C57 mice, whereas the LXR α KO mice showed no change in TAG ratios versus vehicle dosed animals. Measurements of lipid liability in response to an LXR agonist are typically made by measuring total liver TAG levels, which here, only showed a significant effect after the 48 H and 5 day dose regimes. By using a ratio measurement analysis could be performed on plasma samples, greatly simplifying the sample preparation procedure, without the requirement for either calibration curves or an internal standard.     

Determination of the amount of homology required for recombination in bacteriophage T4

Homology is an important feature of recombination. We have used the rll cistrons of bacteriophage T4 to determine the extent of homology required for recombination. We varied the amount of homologous DNA available for recombination in both marker rescue experiments and deletion-by-deletion crosses. Our results suggest that the primary pathway for recombination in T4 requires 50 bp of homology. Our finding that recombination is detectable when fewer than 50 bp of homology are available suggests that there is a second, less efficient pathway of recombination in T4. This pathway may be used during the formation of deletions.     

Cell adhesion molecules, second messengers and axonal growth.

Recent studies on NCAM-related molecules suggest that individual cell adhesion molecules might function to both promote axonal growth during development and maintain synaptic structure in the adult. Evidence that differential alternative splicing contributes to this apparent bifunctionality of cell adhesion molecules is discussed.     

The effect of benzoic acid concentration on nitrogen metabolism,manure ammonia and odour emissions in finishing pigs

A complete randomised block design experiment was conducted to investigate the effects of benzoic acid inclusion level on nitrogen (N) metabolism, and manure ammonia (NH₃) and odour emissions in finishing pigs. Sixteen boars (64 kg live weight ± 1.5 kg) were assigned to one of four dietary treatments (T) varying in benzoic acid concentration: (T1) 0 g benzoic acid/kg (as fed); (T2) 10 g benzoic acid/kg; (T3) 20 g benzoic acid/kg; (T4) 30 g benzoic acid/kg. Animals were housed in individual metabolism crates and feed was provided ad libitum. All diets were formulated to have similar concentration of digestible energy and ileal digestible lysine with benzoic acid replacing wheat in the diet. There was a linear decrease in NH₃ emission (P<0.001), as the dietary benzoic acid concentration increased (141.4 mg/g versus 40.5 mg/g N intake (S.E.M. 12.1) over the 240-h storage period). However, there was no effect (P>0.05) of benzoic acid on odour concentration. Urinary nitrogen (N) excretion, total N excretion and the urinary:faecal N ratio were linearly reduced (P<0.05) with increasing benzoic acid inclusion. Furthermore, N retention increased linearly (P<0.05) as benzoic acid concentration increased from 0 g/kg to 30 g/kg in the diet. In conclusion, the inclusion of benzoic acid in the diet of finishing pigs has the potential to reduce total and urinary N excretion and the urinary to faecal N ratio. This was mirrored by reductions in manure NH₃ emissions in the benzoic acid supplemented treatments.     

Effectiveness of the diabetes education and self management for ongoing and newly diagnosed (DESMOND) programme for people with newly diagnosed type 2 diabetes: cluster randomised controlled trial

Objective To evaluate the effectiveness of a structured group education programme on biomedical, psychosocial, and lifestyle measures in people with newly diagnosed type 2 diabetes.Design Multicentre cluster randomised controlled trial in primary care with randomisation at practice level.Setting 207 general practices in 13 primary care sites in the United Kingdom.Participants 824 adults (55% men, mean age 59.5 years).Intervention A structured group education programme for six hours delivered in the community by two trained healthcare professional educators compared with usual care.Main outcome measures Haemoglobin A_1c levels, blood pressure, weight, blood lipid levels, smoking status, physical activity, quality of life, beliefs about illness, depression, and emotional impact of diabetes at baseline and up to 12 months.Main results Haemoglobin A_1c levels at 12 months had decreased by 1.49% in the intervention group compared with 1.21% in the control group. After adjusting for baseline and cluster, the difference was not significant: 0.05% (95% confidence interval −0.10% to 0.20%). The intervention group showed a greater weight loss: −2.98 kg (95% confidence interval −3.54 to −2.41) compared with 1.86 kg (−2.44 to −1.28), P=0.027 at 12 months. The odds of not smoking were 3.56 (95% confidence interval 1.11 to 11.45), P=0.033 higher in the intervention group at 12 months. The intervention group showed significantly greater changes in illness belief scores (P=0.001); directions of change were positive indicating greater understanding of diabetes. The intervention group had a lower depression score at 12 months: mean difference was −0.50 (95% confidence interval −0.96 to −0.04); P=0.032. A positive association was found between change in perceived personal responsibility and weight loss at 12 months (β=0.12; P=0.008).Conclusion A structured group education programme for patients with newly diagnosed type 2 diabetes resulted in greater improvements in weight loss and smoking cessation and positive improvements in beliefs about illness but no difference in haemoglobin A_1c levels up to 12 months after diagnosis.Trial registration Current Controlled Trials ISRCTN17844016.