Distribution of human beta-defensin polymorphisms in various control and cystic fibrosis populations.

Abstract Human beta defensins contribute to the first line of defense against infection of the lung. Polymorphisms in these genes are therefore potential modifiers of the severity of lung disease in cystic fibrosis. Polymorphisms were sought in the human beta-defensin genes DEFB1, DEFB4, DEFB103A, and DEFB104 in healthy individuals and cystic fibrosis (CF) patients living in various European countries. DEFB1, DEFB4, and DEFB104 were very polymorphic, but DEFB103A was not. Within Europe, differences between control populations were found for some of the frequent polymorphisms in DEFB1, with significant differences between South-Italian and Czech populations. Moreover, frequent polymorphisms located in DEFB4 and DEFB104 were not in Hardy Weinberg equilibrium in all populations studied, while those in DEFB1 were in Hardy Weinberg equilibrium. Sequencing of a monochromosomal chromosome 8 mouse-human hybrid cell line revealed signals for multiple alleles for some loci in DEFB4 and DEFB104, but not for DEFB1. This indicated that more than one DEFB4 and DEFB104 gene was present on this chromosome 8, in agreement with recent findings that DEFB4 and DEFB104 are part of a repeat region. Individual DEFB4 and DEFB104 PCR amplification products of various samples were cloned and sequenced. The results showed that one DNA sample could contain more than two haplotypes, indicating that the various repeats on one chromosome were not identical. Given the higher complexity found in the genomic organization of the DEFB4 and DEFB104 genes, association studies with CF lung disease severity were performed only for frequent polymorphisms located in DEFB1. No association with the age of first infection by Pseudomonas aeruginosa or with the FEV1 percentage at the age of 11-13 years could be found

Skin barrier fine-tuning through low-temperature lipid chain transition

The lipids in the mammalian stratum corneum (SC) adopt an unusually rigid arrangement to form a vital barrier preventing water loss and harmful environmental impacts. Just above the physiological temperature, a subset of barrier lipids undergoes a phase transition from a very tight orthorhombic to a looser hexagonal arrangement and vice versa. The purpose of this lipid transition in skin physiology is unknown. Permeability experiments on isolated human SC indicated that the transition affects the activation energy for a model compound that prefers lateral movement along lipid layers but not for water or a large polymer that would cross the SC via the pore pathway. The orthorhombic phase content of SC lipids, as determined by infrared spectroscopy, was also modulated by (de)hydration. Spontaneous rearrangement of human SC lipid monolayers into 10 nm higher multilamellar islets at 32 – 37°C, but not at room temperature, was revealed by atomic force microscopy. Our findings add to our knowledge of fundamental skin physiology suggesting a fine temperature- and hydration-controlled switch from fluid lipids required for lipid barrier assembly to rigid and tightly packed lipids in the mature SC necessary for the water and permeability barriers

Skin barrier fine-tuning through low-temperature lipid chain transition

The lipids in the mammalian stratum corneum (SC) adopt an unusually rigid arrangement to form a vital barrier preventing water loss and harmful environmental impacts. Just above the physiological temperature, a subset of barrier lipids undergoes a phase transition from a very tight orthorhombic to a looser hexagonal arrangement and vice versa. The purpose of this lipid transition in skin physiology is unknown. Permeability experiments on isolated human SC indicated that the transition affects the activation energy for a model compound that prefers lateral movement along lipid layers but not for water or a large polymer that would cross the SC via the pore pathway. The orthorhombic phase content of SC lipids, as determined by infrared spectroscopy, was also modulated by (de)hydration. Spontaneous rearrangement of human SC lipid monolayers into 10 nm higher multilamellar islets at 32 – 37°C, but not at room temperature, was revealed by atomic force microscopy. Our findings add to our knowledge of fundamental skin physiology suggesting a fine temperature- and hydration-controlled switch from fluid lipids required for lipid barrier assembly to rigid and tightly packed lipids in the mature SC necessary for the water and permeability barriers

Skin barrier fine-tuning through low-temperature lipid chain transition

The lipids in the mammalian stratum corneum (SC) adopt an unusually rigid arrangement to form a vital barrier preventing water loss and harmful environmental impacts. Just above the physiological temperature, a subset of barrier lipids undergoes a phase transition from a very tight orthorhombic to a looser hexagonal arrangement and vice versa. The purpose of this lipid transition in skin physiology is unknown. Permeability experiments on isolated human SC indicated that the transition affects the activation energy for a model compound that prefers lateral movement along lipid layers but not for water or a large polymer that would cross the SC via the pore pathway. The orthorhombic phase content of SC lipids, as determined by infrared spectroscopy, was also modulated by (de)hydration. Spontaneous rearrangement of human SC lipid monolayers into 10 nm higher multilamellar islets at 32 – 37°C, but not at room temperature, was revealed by atomic force microscopy. Our findings add to our knowledge of fundamental skin physiology suggesting a fine temperature- and hydration-controlled switch from fluid lipids required for lipid barrier assembly to rigid and tightly packed lipids in the mature SC necessary for the water and permeability barriers.THIS DATASET IS ARCHIVED AT DANS/EASY, BUT NOT ACCESSIBLE HERE. TO VIEW A LIST OF FILES AND ACCESS THE FILES IN THIS DATASET CLICK ON THE DOI-LINK ABOV