Cone outer segments: a biophysical model of membrane dynamics, shape retention, and lamella formation.

An hypothesis is developed to explain how the unique, right circular conical geometry of cone outer segments (COSs) in Xenopus laevis and other lower vertebrates is maintained during the cycle of axial shortening by apical phagocytosis and axial elongation via the addition of new basal lamellae. Extension of a new basal evagination (BE) applies radial (lateral) traction to membrane and cytoplasmic domains, achieving two coupled effects. 1), The bilayer domain is locally stretched/dilated, creating an entropic driving force that draws membrane components into the BE from the COS's distributed bilayer phase, i.e., plasmalemma and older lamellae (membrane recycling). Membrane proteins, e.g., opsins, are carried passively in this advective, bilayer-driven process. 2), With BE stretching, hydrostatic pressure within the BE cytoplasm is reduced slightly with respect to that of the axonemal cytoplasmic reservoir, allowing cytoplasmic flow into the BE. Attendant lowering of the reservoir's hydrostatic pressure facilitates the subsequent transfer of cytoplasm from lamellar domains to the reservoir (cytoplasmic recycling). The geometry of the BE reflects the membrane/cytoplasm ratio needed for its construction, and essentially specifies the ratio of components recycled from older lamellae. Length and taper angle of the COS reflect the ratio of recycled/new components constructing a new BE. The model also integrates the trajectories and dynamics of lamella open margin lattice components. Although not fully evaluated, the initial model has been assessed against the relevant literature, and three experimental predictions are derived.

A simplified mass-transfer model for visual pigments in amphibian retinal-cone outer segments.

When radiolabeled precursors and autoradiography are used to investigate turnover of protein components in photoreceptive cone outer segments (COSs), the labeled components--primarily visual pigment molecules (opsins)--are diffusely distributed along the COS. To further assess this COS labeling pattern, we derive a simplified mass-transfer model for quantifying the contributions of advective and diffusive mechanisms to the distribution of opsins within COSs of the frog retina. Two opsin-containing regions of the COS are evaluated: the core axial array of disks and the plasmalemma. Numerical solutions of the mass-transfer model indicate three distinct stages of system evolution. In the first stage, plasmalemma diffusion is dominant. In the second stage, the plasmalemma density reaches a metastable state and transfer between the plasmalemma and disk region occurs, which is followed by an increase in density that is qualitatively similar for both regions. The final stage consists of both regions slowly evolving to the steady-state solution. Our results indicate that autoradiographic and cognate approaches for tracking labeled opsins in the COS cannot be effective methodologies for assessing new disk formation at the base of the COS.

Association of Birth Weight with Health and Long-Term Survival up to Middle and Old Ages in China.

This study is based on an unique dataset of birth records of 11,693 persons born in Beijing, China from 1921-54 and from clinical examinations (May 2003-April 2005) of 2,085 tracked surviving cohort members (aged 50-82) to diagnose seven major chronic diseases. Data were analyzed using the extended Fixed Attribute Dynamics (FAD) method and multivariate regressions. The results of our FAD analysis have shown that, as compared to the persons with low birth weight (<2,500 g), the probability of survival from age 0 to ages 50-56, 63-67 and 68-82 for persons with higher birth weight (2,500-2,999 g, 3,000-3499 g, or ≥3,500 g) was 16-31, 62-104, and 52-108% higher respectively. These estimates display similar patterns for both genders, with somewhat stronger effects in men. Of the 27 estimates of the Odds Ratio of Survival in the FAD analysis, 21 are statistically significant. Controlling for 14 confounding factors, multivariate binary logistic regressions have demonstrated that the risk of having cardiovascular disease and diabetes is negatively associated birth weight; ordinal logit regressions have shown that the number of major chronic diseases at ages 50-82 is significantly associated with birth weight: the lower the birth weight, the higher the risk of having more chronic diseases. We conclude that low birth weight is negatively associated with 1) long-term survival probability from age 0 to ages 50-82, and 2) overall health at middle and old ages. Further research is needed to understand the mechanisms of these effects.