Actively Contracting Bundles of Polar Filaments

We introduce a phenomenological model to study the properties of bundles of polar filaments which interact via active elements. The stability of the homogeneous state, the attractors of the dynamics in the unstable regime and the tensile stress generated in the bundle are discussed. We find that the interaction of parallel filaments can induce unstable behavior and is responsible for active contraction and tension in the bundle. Interaction between antiparallel filaments leads to filament sorting. Our model could apply to simple contractile structures in cells such as stress fibers.Comment: 4 pages, 4 figures, RevTex, to appear in Phys. Rev. Let

Walks of molecular motors in two and three dimensions

Molecular motors interacting with cytoskeletal filaments undergo peculiar random walks consisting of alternating sequences of directed movements along the filaments and diffusive motion in the surrounding solution. An ensemble of motors is studied which interacts with a single filament in two and three dimensions. The time evolution of the probability distribution for the bound and unbound motors is determined analytically. The diffusion of the motors is strongly enhanced parallel to the filament. The analytical expressions are in excellent agreement with the results of Monte Carlo simulations.Comment: 7 pages, 2 figures, to be published in Europhys. Let

Change in Cone Structure Over 24 Months in USH2A-Related Retinal Degeneration

Purpose: To describe cone structure changes using adaptive optics scanning laser ophthalmoscopy (AOSLO) in the Rate of Progression of USH2A-related Retinal Degeneration (RUSH2A) study. Design: Multicenter, longitudinal natural history study. Methods: AOSLO images were acquired at 4 centers, twice at baseline and annually for 24 months in this natural history study. For each eye, at least 10 regions of interest (ROIs) with ≥50 contiguous cones were analyzed by masked, independent graders. Cone spacing Z-scores, standard deviations from the normal mean at the measured location, were compared between graders and tests at baseline. The association of cone spacing with clinical characteristics was assessed using linear mixed effects regression models weighted by image quality score. Annual rates of change were calculated based on differences between visits. Results: Fourteen eyes of 14 participants were imaged, with 192 ROIs selected at baseline. There was variability among graders, which was greater in images with lower image quality score (P < .001). Cone spacing was significantly correlated with eccentricity, quality score, and disease duration (P < .02). On average, the cone spacing Z-score increased 0.14 annually (about 9%, P < .001). We observed no significant differences in rate of change between disease type (Usher syndrome or retinitis pigmentosa), imaging site, or grader. Conclusions: Using current methods, the analysis of quantitative measures of cone structure showed some challenges, yet showed promise that AOSLO images can be used to characterize progressive change over 24 months. Additional multicenter studies using AOSLO are needed to advance cone mosaic metrics as sensitive outcome measures for clinical trials

The proangiogenic capacity of polymorphonuclear neutrophils delineated by microarray technique and by measurement of neovascularization in wounded skin of CD18-deficient mice

Growing evidence supports the concept that polymorphonuclear neutrophils (PMN) are critically involved in inflammation-mediated angiogenesis which is important for wound healing and repair. We employed an oligonucleotide microarray technique to gain further insight into the molecular mechanisms underlying the proangiogenic potential of human PMN. In addition to 18 known angiogenesis-relevant genes, we detected the expression of 10 novel genes, namely midkine, erb-B2, ets-1, transforming growth factor receptor-beta(2) and -beta(3), thrombospondin, tissue inhibitor of metalloproteinase 2, ephrin A2, ephrin B2 and restin in human PMN freshly isolated from the circulation. Gene expression was confi rmed by the RT-PCR technique. In vivo evidence for the role of PMN in neovascularization was provided by studying neovascularization in a skin model of wound healing using CD18-deficient mice which lack PMN infi ltration to sites of lesion. In CD18-deficient animals, neo- vascularization was found to be signifi cantly compromised when compared with wild- type control animals which showed profound neovascularization within the granulation tissue during the wound healing process. Thus, PMN infiltration seems to facilitate inflammation mediated angiogenesis which may be a consequence of the broad spectrum of proangiogenic factors expressed by these cells. Copyright (c) 2006 S. Karger AG, Basel