Rhomboid family member 2 regulates cytoskeletal stress-associated Keratin 16.

Keratin 16 (K16) is a cytoskeletal scaffolding protein highly expressed at pressure-bearing sites of the mammalian footpad. It can be induced in hyperproliferative states such as wound healing, inflammation and cancer. Here we show that the inactive rhomboid protease RHBDF2 (iRHOM2) regulates thickening of the footpad epidermis through its interaction with K16. K16 expression is absent in the thinned footpads of irhom2-/- mice compared with irhom2+/+mice, due to reduced keratinocyte proliferation. Gain-of-function mutations in iRHOM2 underlie Tylosis with oesophageal cancer (TOC), characterized by palmoplantar thickening, upregulate K16 with robust downregulation of its type II keratin binding partner, K6. By orchestrating the remodelling and turnover of K16, and uncoupling it from K6, iRHOM2 regulates the epithelial response to physical stress. These findings contribute to our understanding of the molecular mechanisms underlying hyperproliferation of the palmoplantar epidermis in both physiological and disease states, and how this 'stress' keratin is regulated

Modelling the light variability of the Ap star epsilon Ursae Majoris

We simulate the light variability of the Ap star epsUMa using the observed surface distributions of Fe, Cr, Ca, Mn, Mg, Sr and Ti obtained with the help of Doppler Imaging technique. Using all photometric data available we specified light variations of epsUMa modulated by its rotation from far UV to IR. We employed the LLmodels stellar model atmosphere code to predict the light variability in different photometric systems. The rotational period of epsUMa is refined to 5d088631(18). It is shown that the observed light variability can be explained as a result of the redistribution of radiative flux from the UV spectral region to the visual caused by the inhomogeneous surface distribution of chemical elements. Among seven mapped elements, only Fe and Cr significantly contribute to the amplitude of the observed light variability. In general, we find a very good agreement between theory and observations. We confirm the important role of Fe and Cr to the magnitude of the well-known depression around 5200 \AA\ through the analysis of the peculiar $a$-parameter. Finally, we show that the abundance spots of considered elements cannot explain the observed variability in near UV and $\beta$ index which are likely due to some other causes. The inhomogeneous surface distribution of chemical elements can explain most of the observed light variability of the A-type CP star epsUMa.Comment: Accepted in A&A, 10 pages, 9 figures, 3 table

A Comprehensive Spectral and Variability Study of Narrow-Line Seyfert 1 Galaxies Observed by ASCA: II. Spectral Analysis and Correlations

(Abridged) I present a comprehensive and uniform analysis of 25 {\it ASCA} observations from 23 Narrow-line Seyfert 1 galaxies. The spectral analysis and correlations are presented in this paper, Part 2; the reduction and time series analysis is presented in the companion paper, Part 1.Comment: 73 pages, 31 figures, accepted for publication in ApJS. Report also available at http://www.astro.columbia.edu/~leighly/research.htm

Characterising the biophysical properties of normal and hyperkeratotic foot skin

BACKGROUND: Plantar foot skin exhibits unique biophysical properties that are distinct from skin on other areas of the body. This paper characterises, using non-invasive methods, the biophysical properties of foot skin in healthy and pathological states including xerosis, heel fissures, calluses and corns. METHODS: Ninety three people participated. Skin hydration, elasticity, collagen and elastin fibre organisation and surface texture was measured from plantar calluses, corns, fissured heel skin and xerotic heel skin. Previously published criteria were applied to classify the severity of each skin lesion and differences in the biophysical properties compared between each classification. RESULTS: Calluses, corns, xerotic heel skin and heel fissures had significantly lower levels of hydration; less elasticity and greater surface texture than unaffected skin sites (p < 0.01). Some evidence was found for a positive correlation between hydration and elasticity data (r ≤ 0.65) at hyperkeratotic sites. Significant differences in skin properties (with the exception of texture) were noted between different classifications of skin lesion. CONCLUSIONS: This study provides benchmark data for healthy and different severities of pathological foot skin. These data have applications ranging from monitoring the quality of foot skin, to measuring the efficacy of therapeutic interventions. KEYWORDS: Biophysical parameters; Callus; Corns; Dry skin; Heel fissures; Plantar foot skin hyperkeratosis; Quantification; Skin classification (SELs); Xerosi

Of monkeys and men:Impatience in perceptual decision-making

For decades sequential sampling models have successfully accounted for human and monkey decision-making, relying on the standard assumption that decision makers maintain a pre-set decision standard throughout the decision process. Based on the theoretical argument of reward rate maximization, some authors have recently suggested that decision makers become increasingly impatient as time passes and therefore lower their decision standard. Indeed, a number of studies show that computational models with an impatience component provide a good fit to human and monkey decision behavior. However, many of these studies lack quantitative model comparisons and systematic manipulations of rewards. Moreover, the often-cited evidence from single-cell recordings is not unequivocal and complimentary data from human subjects is largely missing. We conclude that, despite some enthusiastic calls for the abandonment of the standard model, the idea of an impatience component has yet to be fully established; we suggest a number of recently developed tools that will help bring the debate to a conclusive settlement

The human keratins: biology and pathology

The keratins are the typical intermediate filament proteins of epithelia, showing an outstanding degree of molecular diversity. Heteropolymeric filaments are formed by pairing of type I and type II molecules. In humans 54 functional keratin genes exist. They are expressed in highly specific patterns related to the epithelial type and stage of cellular differentiation. About half of all keratins—including numerous keratins characterized only recently—are restricted to the various compartments of hair follicles. As part of the epithelial cytoskeleton, keratins are important for the mechanical stability and integrity of epithelial cells and tissues. Moreover, some keratins also have regulatory functions and are involved in intracellular signaling pathways, e.g. protection from stress, wound healing, and apoptosis. Applying the new consensus nomenclature, this article summarizes, for all human keratins, their cell type and tissue distribution and their functional significance in relation to transgenic mouse models and human hereditary keratin diseases. Furthermore, since keratins also exhibit characteristic expression patterns in human tumors, several of them (notably K5, K7, K8/K18, K19, and K20) have great importance in immunohistochemical tumor diagnosis of carcinomas, in particular of unclear metastases and in precise classification and subtyping. Future research might open further fields of clinical application for this remarkable protein family

A novel keratin 12 mutation in a German kindred with Meesmann's corneal dystrophy

AIM—To study a kindred with Meesmann's corneal dystrophy (MCD) to determine if a mutation within the cornea specific K3 or K12 genes is responsible for the disease phenotype.
METHODS—Slit lamp examination of the cornea in four members of the kindred was carried out to confirm the diagnosis of MCD. The region encoding the helix initiation motif (HIM) of the K12 polypeptide was polymerase chain reaction (PCR) amplified from genomic DNA derived from affected individuals in the kindred. PCR products generated were subjected to direct automated sequencing. Restriction enzyme analysis employing Ban I was used to confirm the presence of the mutation in affected individuals of the family.
RESULTS—Sequencing of the K12 gene in an affected individual from the family revealed a novel heterozygous missense mutation (413A→C), predicting the substitution of a proline for a glutamine at codon 130 (Q130P) in the HIM of the K12 protein. The mutation was excluded from 50 normal, unaffected individuals by restriction enyzme analysis and was therefore unlikely to be a common polymorphism.
CONCLUSION—A novel missense mutation in the K12 gene leads to MCD in a German kindred. Missense mutations have now been identified within the region encoding the helix initiation motif of the K12 protein in eight of 11 MCD kindreds analysed at the molecular level.