In eukaryotic cells, the internalization of extracellular cargo via the endocytic machinery is an important regulatory process required for many essential cellular functions. The role of cooperative protein-protein and protein-membrane interactions in the ubiquitous endocytic pathway in mammalian cells, namely the clathrin-dependent endocytosis, remains unresolved. We employ the Helfrich membrane Hamiltonian together with surface evolution methodology to address how the shapes and energetics of vesicular-bud formation in a planar membrane are stabilized by presence of the clathrin-coat assembly. Our results identify a unique dual role for the tubulating protein epsin: multiple epsins localized spatially and orientationally collectively play the role of a curvature inducing capsid; in addition, epsin serves the role of an adapter in binding the clathrin coat to the membrane. Our results also suggest an important role for the clathrin lattice, namely in the spatial- and orientational-templating of epsins. We suggest that there exists a critical size of the coat above which a vesicular bud with a constricted neck resembling a mature vesicle is stabilized. Based on the observed strong dependence of the vesicle diameter on the bending rigidity, we suggest that the variability in bending stiffness due to variations in membrane composition with cell type can explain the experimentally observed variability on the size of clathrin-coated vesicles, which typically range 50–100 nm. Our model also provides estimates for the number of epsins involved in stabilizing a coated vesicle, and without any direct fitting reproduces the experimentally observed shapes of vesicular intermediates as well as their probability distributions quantitatively, in wildtype as well as CLAP IgG injected neuronal cell experiments. We have presented a minimal mesoscale model which quantitatively explains several experimental observations on the process of vesicle nucleation induced by the clathrin-coated assembly prior to vesicle scission in clathrin dependent endocytosis.
The Severity of Alopecia Tool serves as a tool for alopecia research and a clinical guideline for following progression of disease. The original Severity of Alopecia Tool score does not take into account pediatric age groups. As new clinical trials for alopecia areata include more children, a more accurate tool should be available for this population. By collecting images from patients 2-21 years of age and aligning the hair-bearing regions of the scalp, we created an adaptation of the Severity of Alopecia Tool for scoring hair loss percentage of the top, parietal, and occipital scalp in individuals 2-5, 6-11, and 12-21 years of age.The Severity of Alopecia Tool (SALT) has served as a guideline for alopecia research since its introduction at a National Alopecia Areata (Figure 1). We adapted the original SALT percentages for the pediatric scalp and propose calling this the pediatric Severity of Alopecia Tool (pSALT).To assess the hypothesis that SALT scores do not reflect surface area for children's heads, we collected 400 images from 85 children with alopecia areata 2-5 (n = 25), 6-11 (n = 30), and 12-21 (n = 30) years of age taken from four views (top, back, right, left scalp).F I G U R E 1 Variations in head proportions in different age groups. Left: Standard proportions of the human skull from anatomy guidelines (Reproduced with permission from Elsevier for Burdi AR, Huelke RG, Synder GH, et al., 1969). Right (A) shows head mask probabilities for children ages 2-5 years, (B) for children 6-11 years, and (C) for children 12 years and older.
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