Commercial weight loss diets meet nutrient requirements in free living adults over 8 weeks: A randomised controlled weight loss trial

Objective: To investigate the effect of commercial weight loss programmes on macronutrient composition and micronutrient adequacy over a 2 month period

Systems analysis of apoptosis protein expression allows the case-specific prediction of cell death responsiveness of melanoma cells.

Many cancer entities and their associated cell line models are highly heterogeneous in their responsiveness to apoptosis inducers and, despite a detailed understanding of the underlying signaling networks, cell death susceptibility currently cannot be predicted reliably from protein expression profiles. Here, we demonstrate that an integration of quantitative apoptosis protein expression data with pathway knowledge can predict the cell death responsiveness of melanoma cell lines. By a total of 612 measurements, we determined the absolute expression (nM) of 17 core apoptosis regulators in a panel of 11 melanoma cell lines, and enriched these data with systems-level information on apoptosis pathway topology. By applying multivariate statistical analysis and multi-dimensional pattern recognition algorithms, the responsiveness of individual cell lines to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) or dacarbazine (DTIC) could be predicted with very high accuracy (91 and 82% correct predictions), and the most effective treatment option for individual cell lines could be pre-determined in silico. In contrast, cell death responsiveness was poorly predicted when not taking knowledge on protein-protein interactions into account (55 and 36% correct predictions). We also generated mathematical predictions on whether anti-apoptotic Bcl-2 family members or x-linked inhibitor of apoptosis protein (XIAP) can be targeted to enhance TRAIL responsiveness in individual cell lines. Subsequent experiments, making use of pharmacological Bcl-2/Bcl-xL inhibition or siRNA-based XIAP depletion, confirmed the accuracy of these predictions. We therefore demonstrate that cell death responsiveness to TRAIL or DTIC can be predicted reliably in a large number of melanoma cell lines when investigating expression patterns of apoptosis regulators in the context of their network-level interplay. The capacity to predict responsiveness at the cellular level may contribute to personalizing anti-cancer treatments in the future

An investigation of the efficacy of low carbohydrate diets, with and without exercise, and the implications of this weight loss approach for body composition and cardiovascular disease risk

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

An Investigation of The Efficacy of Low Carbohydrate Diets, With and Without Exercise, and The Implications of This Weight Loss Approach For Body Composition and Cardiovascular Disease Risk.

As the obesity epidemic continues unabated, further investigation of novel weight loss approaches is warranted. Low carbohydrate diets (LCDs) provide one possible dietary strategy for weight loss. This thesis addresses continuing concerns regarding this weight loss approach by comphrensively investigating LCDs. The effects of a LCD, with and without exercise, on CVD risk factors was investigated in a 6 month randomised study. Fifty-six overweight or obese men were instructed to follow a LCD whilst either increasing or maintaining baseline activity levels (Chapter 3). Results demonstrated LCDs to be a safe and effective weight loss strategy with no significant additive effects of exercise seen. Low levels of compliance to exercise instructions were evident therefore subjects were regrouped according to reported exercise levels (Chapter 4). An additive effect on the reduction of weight, body fat mass, diastolic blood pressure, glycaemic response and C-reactive protein (CRP) was seen in subjects who reported increasing activity levels. In order to elucidate the nature and extent of the rapid initial weight loss associated with LCDs a second study investigated the early changes in weight and body composition (Chapter 5). Overweight or obese women (n=17) followed a LCD for 8 weeks with rapid initial weight loss observed and body fat reduced from the outset. Finally, a systematic review with a meta-analysis was conducted to assess the current evidence investigating the efficacy and CVD risk of reduced carbohydrate diets with exercise as a weight loss intervention (Chapter 6). No significant added effect of exercise on weight loss or CVD risk reduction was seen. This evidence demonstrates that LCDs are an effective means of reducing adiposity and inducing positive effects across numerous CVD risk factors. Regular but modest amounts of exercise may induce additional positive effects on weight and CVD risk. Therefore a whole lifestyle approach incorporating a LCD with exercise is an efficacious alternative to more conventional weight loss strategies