Obesity, smoking, alcohol consumption and years lived with disability: A Sullivan life table approach

Background: To avoid strong declines in the quality of life due to population ageing, and to ensure sustainability of the health care system, reductions in the burden of disability among elderly populations are urgently needed. Life style interventions may help to reduce the years lived with one or more disabilities, but it is not fully understood which life style factor has the largest potential for such reductions. Therefore, the primary aim of this paper is to compare the effect of BMI, smoking and alcohol consumption on life expectancy with disability, using the Sullivan life table method. A secondary aim is to assess potential improvement of the Sullivan method by using information on the association of disability with time to death. Methods. Data from the Dutch Permanent Survey of the Living Situation (POLS) 1997-1999 with mortality follow-up until 2006 (n = 6,446) were used. Using estimated relative mortality risks by risk factor exposure, separate life tables were constructed for groups defined in terms of BMI, smoking status and alcohol consumption. Logistic regression models were fitted to predict the prevalence of ADL and mobility disabilities in relationship to age and risk factor exposure. Using the Sullivan method, predicted age-specific prevalence rates were included in the life table to calculate years lived with disability at age 55. In further analysis we assessed whether adding information on time to death in both the regression models and the life table estimates would lead to substantive changes in the results. Results: Life expectancy at age 55 differed by 1.4 years among groups defined in terms of BMI, 4.0 years by smoking status, and 3.0 years by alcohol consumption. Years lived with disability differed by 2.8 years according to BMI, 0.2 years by smoking and 1.6 by alcohol consumption. Obese persons could expect to live more years with disability (5.9 years) than smokers (3.8 years) and drinkers (3.1 years). Employing information on time to death led to lower estimates of years lived with disability, and to smaller differences in these years according to BMI (2.1 years), alcohol (1.2 years), and smoking (0.1 years). Conclusions: Compared with smoking and drinking alcohol, obesity is most strongly associated with an increased risk of spending many years of life with disability. Although employing information on the relation of disability with time to death improves the precision of Sullivan life table estimates, the relative importance of risk factors remained unchanged

NGF Causes TrkA to Specifically Attract Microtubules to Lipid Rafts

Membrane protein sorting is mediated by interactions between proteins and lipids. One mechanism that contributes to sorting involves patches of lipids, termed lipid rafts, which are different from their surroundings in lipid and protein composition. Although the nerve growth factor (NGF) receptors, TrkA and p75NTR collaborate with each other at the plasma membrane to bind NGF, these two receptors are endocytosed separately and activate different cellular responses. We hypothesized that receptor localization in membrane rafts may play a role in endocytic sorting. TrkA and p75NTR both reside in detergent-resistant membranes (DRMs), yet they responded differently to a variety of conditions. The ganglioside, GM1, caused increased association of NGF, TrkA, and microtubules with DRMs, but a decrease in p75NTR. When microtubules were induced to polymerize and attach to DRMs by in vitro reactions, TrkA, but not p75NTR, was bound to microtubules in DRMs and in a detergent-resistant endosomal fraction. NGF enhanced the interaction between TrkA and microtubules in DRMs, yet tyrosine phosphorylated TrkA was entirely absent in DRMs under conditions where activated TrkA was detected in detergent-sensitive membranes and endosomes. These data indicate that TrkA and p75NTR partition into membrane rafts by different mechanisms, and that the fraction of TrkA that associates with DRMs is internalized but does not directly form signaling endosomes. Rather, by attracting microtubules to lipid rafts, TrkA may mediate other processes such as axon guidance

Scanning a DNA molecule for bound proteins using hybrid magnetic and optical tweezers

The functional state of the genome is determined by its interactions with proteins that bind, modify, and move along the DNA. To determine the positions and binding strength of proteins localized on DNA we have developed a combined magnetic and optical tweezers apparatus that allows for both sensitive and label-free detection. A DNA loop, that acts as a scanning probe, is created by looping an optically trapped DNA tether around a DNA molecule that is held with magnetic tweezers. Upon scanning the loop along the ?-DNA molecule, EcoRI proteins were detected with ?17 nm spatial resolution. An offset of 33±5 nm for the detected protein positions was found between back and forwards scans, corresponding to the size of the DNA loop and in agreement with theoretical estimates. At higher applied stretching forces, the scanning loop was able to remove bound proteins from the DNA, showing that the method is in principle also capable of measuring the binding strength of proteins to DNA with a force resolution of 0.1 pN/[Formula: see text]. The use of magnetic tweezers in this assay allows the facile preparation of many single-molecule tethers, which can be scanned one after the other, while it also allows for direct control of the supercoiling state of the DNA molecule, making it uniquely suitable to address the effects of torque on protein-DNA interactions.BN/BionanoscienceApplied Science