Large-Scale Cortical Functional Organization and Speech Perception across the Lifespan

Aging is accompanied by substantial changes in brain function, including functional reorganization of large-scale brain networks. Such differences in network architecture have been reported both at rest and during cognitive task performance, but an open question is whether these age-related differences show task-dependent effects or represent only task-independent changes attributable to a common factor (i.e., underlying physiological decline). To address this question, we used graph theoretic analysis to construct weighted cortical functional networks from hemodynamic (functional MRI) responses in 12 younger and 12 older adults during a speech perception task performed in both quiet and noisy listening conditions. Functional networks were constructed for each subject and listening condition based on inter-regional correlations of the fMRI signal among 66 cortical regions, and network measures of global and local efficiency were computed. Across listening conditions, older adult networks showed significantly decreased global (but not local) efficiency relative to younger adults after normalizing measures to surrogate random networks. Although listening condition produced no main effects on whole-cortex network organization, a significant age group x listening condition interaction was observed. Additionally, an exploratory analysis of regional effects uncovered age-related declines in both global and local efficiency concentrated exclusively in auditory areas (bilateral superior and middle temporal cortex), further suggestive of specificity to the speech perception tasks. Global efficiency also correlated positively with mean cortical thickness across all subjects, establishing gross cortical atrophy as a task-independent contributor to age-related differences in functional organization. Together, our findings provide evidence of age-related disruptions in cortical functional network organization during speech perception tasks, and suggest that although task-independent effects such as cortical atrophy clearly underlie age-related changes in cortical functional organization, age-related differences also demonstrate sensitivity to task domains

Bound Water at Protein-Protein Interfaces: Partners, Roles and Hydrophobic Bubbles as a Conserved Motif

Background There is a great interest in understanding and exploiting protein-protein associations as new routes for treating human disease. However, these associations are difficult to structurally characterize or model although the number of X-ray structures for protein-protein complexes is expanding. One feature of these complexes that has received little attention is the role of water molecules in the interfacial region. Methodology A data set of 4741 water molecules abstracted from 179 high-resolution (≤ 2.30 Å) X-ray crystal structures of protein-protein complexes was analyzed with a suite of modeling tools based on the HINT forcefield and hydrogen-bonding geometry. A metric termed Relevance was used to classify the general roles of the water molecules. Results The water molecules were found to be involved in: a) (bridging) interactions with both proteins (21%), b) favorable interactions with only one protein (53%), and c) no interactions with either protein (26%). This trend is shown to be independent of the crystallographic resolution. Interactions with residue backbones are consistent for all classes and account for 21.5% of all interactions. Interactions with polar residues are significantly more common for the first group and interactions with non-polar residues dominate the last group. Waters interacting with both proteins stabilize on average the proteins\u27 interaction (−0.46 kcal mol−1), but the overall average contribution of a single water to the protein-protein interaction energy is unfavorable (+0.03 kcal mol−1). Analysis of the waters without favorable interactions with either protein suggests that this is a conserved phenomenon: 42% of these waters have SASA ≤ 10 Å2 and are thus largely buried, and 69% of these are within predominantly hydrophobic environments or “hydrophobic bubbles”. Such water molecules may have an important biological purpose in mediating protein-protein interactions

Migration Flows: Measurement, Analysis and Modeling

This chapter is an introduction to the study of migration flows. It starts with a review of major definition and measurement issues. Comparative studies of migration are particularly difficult because different countries define migration differently and measurement methods are not harmonized. Insight in data collection practices is a first requirement to study flows. In the paper, several migration indicators are presented that describe the level and direction of migration. Scientists attempt to model migration flows since Ravenstein presented his migration laws at the end of the nineteenth century. Initially theories and models were borrowed from physics. The gravity model, based on Newton’s law of gravitation, has been the main model of migration flows for decades and continues to be popular today. Gradually human behaviour replaced the laws of physics and spatial interaction models the gravity model. Spatial interaction models emphasize interaction between geographically dispersed populations. Initially the gravity model had a strong influence on spatial interaction models, but the interest shifted gradually to probability theory and probability models. A parallel development was the life course perspective on migration, resulting from the increased awareness that some life events trigger migration and that during some stages of life, a person has an elevated propensity to migrate. These links produce the typical and universal age patterns of migration. Today, population projection models incorporate models of these typical age patterns (model schedules) and models of spatial interaction. Projection models may be turned into policy models to infer the migration flows required to meet demographic objectives, i.e. to offset population decline resulting from low fertility

Migration Systems in Europe: Evidence From Harmonized Flow Data

Empirical tests of migration systems theory require consistent and complete data on international migration flows. Publicly available data, however, represent an inconsistent and incomplete set of measurements obtained from a variety of national data collection systems. We overcome these obstacles by standardizing the available migration reports of sending and receiving countries in the European Union and Norway each year from 2003–2007 and by estimating the remaining missing flows. The resulting harmonized estimates are then used to test migration systems theory. First, locating thresholds in the size of flows over time, we identify three migration systems within the European Union and Norway. Second, examining the key determinants of flows with respect to the predictions of migration systems theory, our results highlight the importance of shared experiences of nation-state formation, geography, and accession status in the European Union. Our findings lend support to migration systems theory and demonstrate that knowledge of migration systems may improve the accuracy of migration forecasts toward managing the impacts of migration as a source of social change in Europe