Complex responses to a diverse environment

A report on the Keystone Symposium 'Innate Immunity: Signaling Mechanisms', Keystone, USA, 24-29 February, 2008

Synchronous vs Asynchronous Chain Motion in α-Synuclein Contact Dynamics

α-Synuclein (α-syn) is an intrinsically unstructured 140-residue neuronal protein of uncertain function that is implicated in the etiology of Parkinson’s disease. Tertiary contact formation rate constants in α-syn, determined from diffusion-limited electron-transfer kinetics measurements, are poorly approximated by simple random polymer theory. One source of the discrepancy between theory and experiment may be that interior-loop formation rates are not well approximated by end-to-end contact dynamics models. We have addressed this issue with Monte Carlo simulations to model asynchronous and synchronous motion of contacting sites in a random polymer. These simulations suggest that a dynamical drag effect may slow interior-loop formation rates by about a factor of 2 in comparison to end-to-end loops of comparable size. The additional deviations from random coil behavior in α-syn likely arise from clustering of hydrophobic residues in the disordered polypeptide

Interrelations among Immune Defense Indexes Reflect Major Components of the Immune System in a Free-Living Vertebrate

Understanding the relationships among immune components in free-living animals is a challenge in ecoimmunology, and it is important not only for selecting the immune assays to be used but also for more knowledgeable interpretation of results. In this study, we investigated the relationships among six immune defense indexes commonly used by ecoimmunologists and measured simultaneously in individual free-living tree swallows. Three main axes of variation in immune function were identified using a principal components analysis, representing variation in T-cell, B-cell, and innate immunity. Measures within each axis tended to be positively correlated among individuals, while measures in different axes were uncorrelated. A trade-off between T-cell function and B-cell function became apparent only when variation among individuals in body condition, age, and general quality was taken into account. Interestingly, the level of natural antibodies, a component of innate immunity, showed the strongest association with components of acquired B-cell function, possibly reflecting a common underlying genetic mechanism, as has been documented in poultry. Our results indicate that despite the complexity of the immune system, important insights can be gained by using the currently available assays but in a more comprehensive approach than has generally been used in the field of ecoimmunology

Cardio-metabolic impact of changing sitting, standing, and stepping in the workplace

According to cross-sectional and acute experimental evidence, reducing sitting time should improve cardio-metabolic health risk biomarkers. Furthermore, the improvements obtained may depend on whether sitting is replaced with standing or ambulatory activities. Based on data from the Stand Up Victoria multi-component workplace intervention, we examined this issue using compositional data analysis - a method that can examine and compare all activity changes simultaneously.Participants receiving the intervention (n=136 ≥0.6 full-time equivalent desk-based workers, 65% women, mean±SD age=44.6 ±9.1 years from seven worksites) were asked to improve whole-of-day activity by standing up, sitting less and moving more. Their changes in the composition of daily waking hours (activPAL-assessed sitting, standing, stepping) were quantified, then tested for associations with concurrent changes in cardio-metabolic risk (CMR) scores and 14 biomarkers concerning body composition, glucose, insulin and lipid metabolism. Analyses were by mixed models, accounting for clustering (3 months, n=105-120; 12 months, n=80-97).Sitting reduction was significantly (

Atomic Resonance and Scattering

Contains research objectives, summary of research and reports on three research projects.U. S. Navy (Office of Naval Research) under Contract N00014-67-A-0204-0006Joint Services Electronics Programs (U. S. Army, U.S. Navy, and U. S. Air Force) under Contract DA 28-043-AMC-02536(E

Materials for stem cell factories of the future

The materials community is now identifying polymeric substrates that could permit translation of human pluripotent stem cells (hPSCs) from lab-based research to industrial scale biomedicine. Well defined materials are required to allow cell banking and to provide the raw material for reproducible differentiation into lineages for large scale drug screening programs and clinical use, wherein >1 billion cells for each patient are needed to replace losses during heart attack, multiple sclerosis and diabetes. Producing this number of cells for one patient is challenging and a rethink is needed to scalable technology with the potential to meet the needs of millions of patients a year. Here we consider the role of materials discovery, an emerging area of materials chemistry that is in a large part driven by the challenges posed by biologists to materials scientists1-4

A Comparison of U. S. and European University-Industry Relations in the Life Sciences

We draw on diverse data sets to compare the institutional organization of upstream life science research across the United States and Europe. Understanding cross-national differences in the organization of innovative labor in the life sciences requires attention to the structure and evolution of biomedical networks involving public research organizations (universities, government laboratories, nonprofit research institutes, and research hospitals), science-based biotechnology firms, and multinational pharmaceutical corporations. We use network visualization methods and correspondence analyses to demonstrate that innovative research in biomedicine has its origins in regional clusters in the United States and in European nations. But the scientific and organizational composition of these regions varies in consequential ways. In the United States, public research organizations and small firms conduct R&D across multiple therapeutic areas and stages of the development process. Ties within and across these regions link small firms and diverse public institutions, contributing to the development of a robust national network. In contrast, the European story is one of regional specialization with a less diverse group of public research organizations working in a smaller number of therapeutic areas. European institutes develop local connections to small firms working on similar scientific problems, while cross-national linkages of European regional clusters typically involve large pharmaceutical corporations. We show that the roles of large and small firms differ in the United States and Europe, arguing that the greater heterogeneity of the U. S. system is based on much closer integration of basic science and clinical development