Disruption of tuftelin 1, a desmosome associated protein, causes skin fragility, woolly hair and palmoplantar keratoderma

Desmosomes are dynamic complex protein structures involved in cellular adhesion. Disruption of these structures by loss of function variants in desmosomal genes lead to a variety of skin and heart related phenotypes. Here, we report tuftelin 1 as a desmosome-associated protein, implicated in epidermal integrity. In two siblings with mild skin fragility, woolly hair and mild palmoplantar keratoderma, but without a cardiac phenotype, we identified a homozygous splice site variant in the TUFT1 gene, leading to aberrant mRNA splicing and loss of tuftelin 1 protein. Patients' skin and keratinocytes showed acantholysis, perinuclear retraction of intermediate filaments, and reduced mechanical stress resistance. Immunolabeling and transfection studies showed that tuftelin 1 is positioned within the desmosome and its location dependent on the presence of the desmoplakin carboxy-terminal tail. A Tuft1 knock-out mouse model mimicked the patients' phenotypes. Altogether, this study reveals tuftelin 1 as a desmosome-associated protein, whose absence causes skin fragility, woolly hair and palmoplantar keratoderma

Disruption of tuftelin 1, a desmosome associated protein, causes skin fragility, woolly hair and palmoplantar keratoderma

Desmosomes are dynamic complex protein structures involved in cellular adhesion. Disruption of these structures by loss of function variants in desmosomal genes lead to a variety of skin and heart related phenotypes. Here, we report tuftelin 1 as a desmosome-associated protein, implicated in epidermal integrity. In two siblings with mild skin fragility, woolly hair and mild palmoplantar keratoderma, but without a cardiac phenotype, we identified a homozygous splice site variant in the TUFT1 gene, leading to aberrant mRNA splicing and loss of tuftelin 1 protein. Patients' skin and keratinocytes showed acantholysis, perinuclear retraction of intermediate filaments, and reduced mechanical stress resistance. Immunolabeling and transfection studies showed that tuftelin 1 is positioned within the desmosome and its location dependent on the presence of the desmoplakin carboxy-terminal tail. A Tuft1 knock-out mouse model mimicked the patients' phenotypes. Altogether, this study reveals tuftelin 1 as a desmosome-associated protein, whose absence causes skin fragility, woolly hair and palmoplantar keratoderma.</p

A quantitative hydrogeomorphic approach to the classification of temporary wetlands in the Doñana National Park (SW Spain)

12 páginas, 3 figuras, 3 tablas, 36 referencias, 1 apéndice: 2 anexos.A quantitative hydrogeomorphic approach was applied to an extensive survey of temporary wetlands in the Doñana National Park (SW Spain) in search for quantitative thresholds for wetland classification. Twenty freshwater ponds on the aeolian sand mantle and 46 sites on silty-clay substrate, located in the southern marshland, were surveyed during the heaviest rainy period so far recorded (October 1995–September 1997). On average, temporary ponds showed higher water depth, longer flooding period, lower conductivity (\0.5 mS cm-1), lower pH (6.7), lower phosphate concentration (0.4 lM) and amore balanced proportion of Ca2+/Na+ than temporary marshes. During floods, marshland sites exhibited higher water transparency, pH (9.5), alkalinity (3.5 meq l-1), conductivity (8.2 mS cm-1), phosphate concentration (0.7 lM), Na+ and Ca2+ concentrations (97.2 and 3.5 meq l-1, respectively) than ponds. Study sites were significantly segregated (ANOSIM test: R = 0.88, P\0.01, n = 92) in relation to water depth and conductivity. A conductivity of 1.6 mS cm-1 is proposed as a threshold between marshland sites and ponds during floods. Marshland sites were further segregated into two groups (ANOSIM test: R = 0.777, P\0.01, n = 23) according to the Na+/Ca2+ ratio (in meq l-1) at a threshold value of 25. An ordination by PCA showed that five variables grouped 81.4%of the total variance in two axes. The first PCA axis (60.7% of variance) separated temporary wetlands into ponds andmarshland sites according to variables related to substrate and hydrology (Na+/Ca2+ ratio, conductivity, water depth and flooding period). Other variables (e.g., water transparency, alkalinity, pH, submersed macrophyte biomass, phosphate, nitrate and planktonic chlorophyll concentrations) did not produce a significant segregation between marshland and pond sites during floods. Further discrimination within each wetland type was thus not achieved.Financial support came from the Spanish Ministry of the Environment (MMA, project 05/99), CICYT (AMB95-1054) and the Junta de Andalucía (research groups #4086 and 4033).Peer reviewe

Generalizations of Clausen's Formula and algebraic transformations of Calabi-Yau differential equations

We provide certain unusual generalizations of Clausen’s and Orr’s theorems for solutions of fourth-order and fifth-order generalized hypergeometric equations. As an application, we present several examples of algebraic transformations of Calabi–Yau differential equations