Nanoscale patterning with block copolymers

The self-assembly processes of block copolymers offer interesting strategies to create patterns on nanometer length scales. The polymeric constituents, substrate surface properties, and experimental conditions all offer parameters that allow the control and optimization of pattern formation for specific applications. We review how such patterns can be obtained and discuss some potential applications using these patterns as (polymeric) nanostructures or templates, e.g. for nanoparticle assembly. The method offers interesting possibilities in combination with existing high-resolution lithography methods, and could become of particular interest in microtechnology and biosensing

Lipid accumulation in non-adipose tissue and lipotoxicity

Obesity is a well-known risk factor for the development of type 2 diabetes mellitus and cardiovascular disease. importantly, obesity is not only associated with lipid accumulation in adipose tissue, but also in non-adipose tissues. The latter is also known as ectopic lipid accumulation and may be a possible link between obesity and its comorbidities such as insulin resistance, type 2 diabetes mellitus and cardiovascular disease. In skeletal muscle and liver, lipid accumulation has been associated with the development of insulin resistance, an early hallmark of developing type 2 diabetes mellitus. More specifically, accumulation of intermediates of lipid metabolism, such as diacylglycerol (DAG) and Acyl-CoA have been shown to interfere with insulin signaling in these tissues. initially, muscular and hepatic insulin resistance can be overcome by an increased insulin production by the pancreas, resulting in hyperinsulinemia. However, during the progression towards overt type 2 diabetes, pancreatic failure occurs resulting in reduced insulin production. Interestingly, also in the pancreas lipid accumulation has been shown to precede dysfunction. Finally, accumulation of fat in the heart has been associated with cardiac dysfunction and heart failure, which may be an explanation for diabetic cardiomyopathy. Taken together, we conclude that evidence for deleterious effects of lipid accumulation in non-adipose tissue (lipotoxicity) is strong. However, while ample human data is available for skeletal muscle and the liver, future research should focus on lipid accumulation in the pancreas and the heart

Mitochondrial Function and Diabetes: Consequences for Skeletal and Cardiac Muscle Metabolism

SIGNIFICANCE: An early hallmark in the development of type 2 diabetes is the resistance to the effect of insulin in skeletal muscle and in the heart. Since mitochondrial function was found to be diminished in patients with type 2 diabetes, it was suggested that this defect might be involved in the etiology of insulin resistance. Although several hypotheses were suggested, yet unclear is the mechanistic link between these two phenomena. Recent advances: Herein, we review the evidence for disturbances in mitochondrial function in skeletal muscle and the heart in the diabetic state. Also the mechanisms involved in improving mitochondrial function are considered and, whenever possible, human data is cited. Reported evidence shows that interventions that improve skeletal muscle mitochondrial function also improve insulin sensitivity in humans. In the heart, available data from animal studies suggests that enhancement of mitochondrial function can reverse aging-induced changes in heart function, and can be protective against cardiomyopathy and heart failure. FUTURE DIRECTIONS: Mitochondria and their functions can be targeted with the aim of improving skeletal muscle insulin sensitivity and cardiac function. However, human clinical intervention studies are needed to fully substantiate the potential of mitochondria as a target to prevent cardiometabolic disease

Lipotoxicity in type 2 diabetic cardiomyopathy

As obesity and type 2 diabetes are becoming an epidemic in westernized countries, the incidence and prevalence of obesity- and diabetes-related co-morbidities are increasing. In type 2 diabetes ectopic lipid accumulation in the heart has been associated with cardiac dysfunction and apoptosis, a process termed lipotoxicity. Since cardiovascular diseases are the main cause of death in diabetic patients, diagnosis and treatment become increasingly important. Although ischaemic heart disease is a major problem in diabetes, non-ischaemic heart disease (better known as diabetic cardiomyopathy) becomes increasingly important with respect to the impairment of cardiac function and mortality in type 2 diabetes. The underlying aetiology of diabetic cardiomyopathy is incompletely understood but is beginning to be elucidated. Various mechanisms have been proposed that may lead to lipotoxicity. Therefore, this review will focus on the mechanisms of cardiac lipid accumulation and its relation to the development of cardiomyopathy

MSc-FH in Life Sciences Fachgebiet Industrial Life Sciences startet im September 2009: FH – HES

The field of specialization denominated Industrial Life Sciences is one branch within the MSc in Life Sciences program of the Swiss Universities of Applied Sciences. It encompasses seven specializations, offered on four campuses and covers analytical sciences, chemistry, biotechnology, industrial pharmacy and parts of medicinal technologies/biomedical engineering. The program aims at the development of competencies which enable graduates to take further scientific and technical as well as management responsibilities within the context of an industrial environment. The master thesis is an essential element of the program. It is always integrated into a project of applied research and/or development which is, whenever possible, part of a collaboration with an industrial partner

The insulin-sensitizing effect of rosiglitazone in type 2 diabetes mellitus patients does not require improved in vivo muscle mitochondrial function.

Aims: To investigate whether improved in vivo mitochondrial function in skeletal muscle and intramyocellular lipids (IMCL) contribute to the insulin-sensitizing effect of rosiglitazone. Methods: Eight overweight type 2 diabetic patients (BMI= 29.3 +/- 1.1 kg/m(2)) were treated with rosiglitazone for 8 weeks. Before and after treatment, insulin sensitivity was determined by a hyperinsulinaemic-euglycaemic clamp. Muscular mitochondrial function (half-time of phosphocreatine recovery after exercise) and IMCL content were measured by magnetic resonance spectroscopy. Results: Insulin sensitivity improved after rosiglitazone (GIR: 19.9+/-2.8 to 24.8+/-2.1 micromol/kg/min (P<0.05)). In vivo mitochondrial function (PCr recovery half-time: 23.8+/-3.5 to 20.0+/-1.7 s (P=0.23)) and IMCL content (0.93+/-0.18% to 1.37+/-0.40%, p=0.34) did not change. Interestingly, the changes in PCr half-time correlated/tended to correlate with changes in fasting insulin (R(2)=0.50, P=0.05), and glucose (R(2)=0.43, p=0.08) levels. Changes in PCr half-time did not correlate with changes in GIR (R(2)=0.08, P=0.49). Conclusion: The rosiglitazone-enhanced insulin sensitivity does not require improved muscular mitochondrial function

Substrate utilization and metabolic profile in response to overfeeding with a high-fat diet in South Asian and white men:a sedentary lifestyle study

Background For the same BMI, South Asians have a higher body fat percentage, a higher liver fat content and a more adverse metabolic profile than whites. South Asians may have a lower fat oxidation than whites, which could result in an unfavorable metabolic profile when exposed to increased high-fat foods consumption and decreased physical activity as in current modern lifestyle. Objective To determine substrate partitioning, liver fat accumulation and metabolic profile in South Asian and white men in response to overfeeding with high-fat diet under sedentary conditions in a respiration chamber. Design Ten South Asian men (BMI, 18-29 kg/m(2)) and 10 white men (BMI, 22-33 kg/m(2)), matched for body fat percentage, aged 20-40 year were included. A weight maintenance diet (30% fat, 55% carbohydrate, and 15% protein) was given for 3 days. Thereafter, a baseline measurement of liver fat content (1H-MRS) and blood parameters was performed. Subsequently, subjects were overfed (150% energy requirement) with a high-fat diet (60% fat, 25% carbohydrate, and 15% protein) over 3 consecutive days while staying in a respiration chamber mimicking a sedentary lifestyle. Energy expenditure and substrate use were measured for 3 x 24-h. Liver fat and blood parameters were measured again after the subjects left the chamber. Results The 24-h fat oxidation as a percentage of total energy expenditure did not differ between ethnicities (P = 0.30). Overfeeding increased liver fat content (P = 0.02), but the increase did not differ between ethnicities (P = 0.64). In South Asians, overfeeding tended to increase LDL-cholesterol (P = 0.08), tended to decrease glucose clearance (P = 0.06) and tended to elevate insulin response (P = 0.07) slightly more than whites. Conclusions Despite a similar substrate partitioning and similar accretion of liver fat, overfeeding with high-fat under sedentary conditions tended to have more adverse effects on the lipid profile and insulin sensitivity in South Asians.</p