Nature of curvature coupling of amphiphysin with membranes depends on its bound density

Cells are populated by a vast array of membrane-binding proteins that execute critical functions. Functions, like signaling and intracellular transport, require the abilities to bind to highly curved membranes and to trigger membrane deformation. Among these proteins is amphiphysin 1, implicated in clathrin-mediated endocytosis. It contains a Bin-Amphiphysin-Rvs membrane-binding domain with an N-terminal amphipathic helix that senses and generates membrane curvature. However, an understanding of the parameters distinguishing these two functions is missing. By pulling a highly curved nanotube of controlled radius from a giant vesicle in a solution containing amphiphysin, we observed that the action of the protein depends directly on its density on the membrane. At low densities of protein on the nearly flat vesicle, the distribution of proteins and the mechanical effects induced are described by a model based on spontaneous curvature induction. The tube radius and force are modified by protein binding but still depend on membrane tension. In the dilute limit, when practically no proteins were present on the vesicle, no mechanical effects were detected, but strong protein enrichment proportional to curvature was seen on the tube. At high densities, the radius is independent of tension and vesicle protein density, resulting from the formation of a scaffold around the tube. As a consequence, the scaling of the force with tension is modified. For the entire density range, protein was enriched on the tube as compared to the vesicle. Our approach shows that the strength of curvature sensing and mechanical effects on the tube depends on the protein density.     

Etiology of Anemia Among Infants, School-Aged Children, and Young Non-Pregnant Women in Different Settings of South-Central Cote d'Ivoire

Anemia affects one-quarter of the world''s population, but its etiology remains poorly understood. We determined the prevalence of anemia and studied underlying risk factors in infants (6–23 months), young school-aged children (6–8 years), and young non-pregnant women (15–25 years) in south-central Côte d''Ivoire. Blood, stool, and urine samples were subjected to standardized, quality-controlled methods. We found high prevalence of anemia, malaria, inflammation, and deficiencies of iron, riboflavin, and vitamin A but low prevalence and intensities of soil-transmitted helminth and schistosome infections. Multivariate regression analysis revealed significant associations between anemia and Plasmodium falciparum for infants, inflammation for school-aged children, and cellular iron deficiency for both school-aged children and non-pregnant women. Women with riboflavin deficiency had significantly lower odds of anemia. Our findings call for interventions to protect infants from malaria, improved intake of dietary iron, better access to health care, and health education.     

Adaptive reorganization of cortical networks in Alzheimer’s disease

ObjectiveThe impact of neuronal cell loss associated with Alzheimer’s disease (AD) on the network organization of the brain is poorly understood. Here we investigated whether modifications in resting-state functional connectivity (FC) are associated with cognitive function of AD patients.MethodsHigh-density electroencephalograms (EEGs) were obtained from patients with early stages of AD and elderly healthy controls. Cortical oscillations were reconstructed with an adaptive spatial filter. Maps of imaginary coherence (IC) between brain areas were compared between groups and correlated with cognitive performance.ResultsParietal and medial temporal lobes of AD patients showed a disruption of alpha band FC to the rest of the brain. However, an adaptive extension of the language network to the right hemisphere could be observed in AD patients and was correlated with better verbal fluency. A shift of FC from alpha frequencies to theta frequencies could be observed in a memory network and was associated with better verbal memory performance.ConclusionsNot only dysfunctional but also adaptive network reorganization occurs in early AD.SignificanceThe network mechanisms for preserved cognitive functioning may inform novel treatment strategies for AD in the future.     

Electrocardiographic Abnormalities in Centenarians and Octogenarians: A Case‐Matched Study

Backround: Centenarians have been proposed as a model of successful aging but recent studies suggest a high prevalence of cardiovascular diseases. Some findings on their electrocardiograms (ECGs) are simply age‐related and others mirror underlying diseases. We aimed to identify ECG features truly associated with extreme age. Methods: Retrospective analysis of 55 centenarians hospitalized between January 2000 and June 2010. Each centenarian was matched with three octogenarians according to gender, presence of hypertension, aortic stenosis, heart failure, and ischemic heart disease. Results: A history of hypertension was present in 32 (58%) centenarians, aortic stenosis in 6 (11%), heart failure in 8 (15%), and ischemic heart disease in 6 (11%). Centenarians had a higher heart rate than octogenarians (81 ± 15 bpm vs. 72 ± 15 bpm, respectively, P < 0.001) but were less frequently on beta‐blockers (7% vs. 36%, respectively, P < 0.001). Centenarians displayed more frequently atrial premature beats than octogenarians (18% vs. 3%, respectively, P < 0.001) but tended to have less atrial fibrillation (15% vs. 22% respectively, P = 0.21). Centenarians had more frequently left QRS axis deviation (48% vs. 28%, P = 0.009) and Q waves (14% vs. 1%, P = 0.02). QT interval was more prolonged in centenarians (446 ± 42 ms vs. 429 ± 39 ms, P = 0.008). Two centenarians (4%) and 24 (15%) octogenarians had a strictly normal ECG (P = 0.02). Conclusions: Abnormal ECG is a common finding in centenarians, with different characteristics than in younger elderly individuals. These differences are unrelated to the presence of cardiac diseases.