Generation of NSE-MerCreMer Transgenic Mice with Tamoxifen Inducible Cre Activity in Neurons

To establish a genetic tool for conditional deletion or expression of gene in neurons in a temporally controlled manner, we generated a transgenic mouse (NSE-MerCreMer), which expressed a tamoxifen inducible type of Cre recombinase specifically in neurons. The tamoxifen inducible Cre recombinase (MerCreMer) is a fusion protein containing Cre recombinase with two modified estrogen receptor ligand binding domains at both ends, and is driven by the neural-specific rat neural specific enolase (NSE) promoter. A total of two transgenic lines were established, and expression of MerCreMer in neurons of the central and enteric nervous systems was confirmed. Transcript of MerCreMer was detected in several non-neural tissues such as heart, liver, and kidney in these lines. In the background of the Cre reporter mouse strain Rosa26R, Cre recombinase activity was inducible in neurons of adult NSE-MerCreMer mice treated with tamoxifen by intragastric gavage, but not in those fed with corn oil only. We conclude that NSE-MerCreMer lines will be useful for studying gene functions in neurons for the conditions that Cre-mediated recombination resulting in embryonic lethality, which precludes investigation of gene functions in neurons through later stages of development and in adult

Comparison of high protein and high fiber weight-loss diets in women with risk factors for the metabolic syndrome: a randomized trial

Abstract Background Studies have suggested that moderately high protein diets may be more appropriate than conventional low-fat high carbohydrate diets for individuals at risk of developing the metabolic syndrome and type 2 diabetes. However in most such studies sources of dietary carbohydrate may not have been appropriate and protein intakes may have been excessively high. Thus, in a proof-of-concept study we compared two relatively low-fat weight loss diets - one high in protein and the other high in fiber-rich, minimally processed cereals and legumes - to determine whether a relatively high protein diet has the potential to confer greater benefits. Methods Eighty-three overweight or obese women, 18-65 years, were randomized to either a moderately high protein (30% protein, 40% carbohydrate) diet (HP) or to a high fiber, relatively high carbohydrate (50% carbohydrate, > 35 g total dietary fiber, 20% protein) diet (HFib) for 8 weeks. Energy intakes were reduced by 2000 - 4000 kJ per day in order to achieve weight loss of between 0.5 and 1 kg per week. Results Participants on both diets lost weight (HP: -4.5 kg [95% confidence interval (CI):-3.7, -5.4 kg] and HFib: -3.3 kg [95% CI: -4.2, -2.4 kg]), and reduced total body fat (HP: -4.0 kg [5% CI:-4.6, -3.4 kg] and HFib: -2.5 kg [95% CI: -3.5, -1.6 kg]), and waist circumference (HP: -5.4 cm [95% CI: -6.3, -4.5 cm] and HFib: -4.7 cm [95% CI: -5.8, -3.6 cm]), as well as total and LDL cholesterol, triglycerides, fasting plasma glucose and blood pressure. However participants on HP lost more body weight (-1.3 kg [95% CI: -2.5, -0.1 kg; p = 0.039]) and total body fat (-1.3 kg [95% CI: -2.4, -0.1; p = 0.029]). Diastolic blood pressure decreased more on HP (-3.7 mm Hg [95% CI: -6.2, -1.1; p = 0.005]). Conclusions A realistic high protein weight-reducing diet was associated with greater fat loss and lower blood pressure when compared with a high carbohydrate, high fiber diet in high risk overweight and obese women.</p

Comparison of high protein and high fiber weight-loss diets in women with risk factors for the metabolic syndrome: A randomized trial

Background: Studies have suggested that moderately high protein diets may be more appropriate than conventional low-fat high carbohydrate diets for individuals at risk of developing the metabolic syndrome and type 2 diabetes. However in most such studies sources of dietary carbohydrate may not have been appropriate and protein intakes may have been excessively high. Thus, in a proof-of-concept study we compared two relatively low-fat weight loss diets - one high in protein and the other high in fiber-rich, minimally processed cereals and legumes - to determine whether a relatively high protein diet has the potential to confer greater benefits. Methods. Eighty-three overweight or obese women, 18-65 years, were randomized to either a moderately high protein (30% protein, 40% carbohydrate) diet (HP) or to a high fiber, relatively high carbohydrate (50% carbohydrate, > 35 g total dietary fiber, 20% protein) diet (HFib) for 8 weeks. Energy intakes were reduced by 2000 - 4000 kJ per day in order to achieve weight loss of between 0.5 and 1 kg per week. Results: Participants on both diets lost weight (HP: -4.5 kg [95% confidence interval (CI):-3.7, -5.4 kg] and HFib: -3.3 kg [95% CI: -4.2, -2.4 kg]), and reduced total body fat (HP: -4.0 kg [5% CI:-4.6, -3.4 kg] and HFib: -2.5 kg [95% CI: -3.5, -1.6 kg]), and waist circumference (HP: -5.4 cm [95% CI: -6.3, -4.5 cm] and HFib: -4.7 cm [95% CI: -5.8, -3.6 cm]), as well as total and LDL cholesterol, triglycerides, fasting plasma glucose and blood pressure. However participants on HP lost more body weight (-1.3 kg [95% CI: -2.5, -0.1 kg; p = 0.039]) and total body fat (-1.3 kg [95% CI: -2.4, -0.1; p = 0.029]). Diastolic blood pressure decreased more on HP (-3.7 mm Hg [95% CI: -6.2, -1.1; p = 0.005]). Conclusions: A realistic high protein weight-reducing diet was associated with greater fat loss and lower blood pressure when compared with a high carbohydrate, high fiber diet in high risk overweight and obese women. © 2011 Te Morenga et al; licensee BioMed Central Ltd

A germ line mutation in cathepsin B points toward a role in asparaginase pharmacokinetics

Contains fulltext : 136201.pdf (publisher's version ) (Closed access