Mutations in Three Genes Encoding Proteins Involved in Hair Shaft Formation Cause Uncombable Hair Syndrome.

Uncombable hair syndrome (UHS), also known as "spun glass hair syndrome," "pili trianguli et canaliculi," or "cheveux incoiffables" is a rare anomaly of the hair shaft that occurs in children and improves with age. UHS is characterized by dry, frizzy, spangly, and often fair hair that is resistant to being combed flat. Until now, both simplex and familial UHS-affected case subjects with autosomal-dominant as well as -recessive inheritance have been reported. However, none of these case subjects were linked to a molecular genetic cause. Here, we report the identification of UHS-causative mutations located in the three genes PADI3 (peptidylarginine deiminase 3), TGM3 (transglutaminase 3), and TCHH (trichohyalin) in a total of 11 children. All of these individuals carry homozygous or compound heterozygous mutations in one of these three genes, indicating an autosomal-recessive inheritance pattern in the majority of UHS case subjects. The two enzymes PADI3 and TGM3, responsible for posttranslational protein modifications, and their target structural protein TCHH are all involved in hair shaft formation. Elucidation of the molecular outcomes of the disease-causing mutations by cell culture experiments and tridimensional protein models demonstrated clear differences in the structural organization and activity of mutant and wild-type proteins. Scanning electron microscopy observations revealed morphological alterations in hair coat of Padi3 knockout mice. All together, these findings elucidate the molecular genetic causes of UHS and shed light on its pathophysiology and hair physiology in general.

Simultaneous imaging and chemical attack of a single living cell within a confluent cell monolayer by means of scanning electrochemical microscopy.

Epithelial cell monolayers from rat kidney were imaged by scanning electrochemical microscopy (SECM) with sub-micrometer resolution in both lateral and vertical direction. Platinum disk ultra-microelectrodes (UMEs) with effective electrode radii between 200 and 600 nm were operated in the constant-height mode. The quality of the recorded SECM images compare favorably with those of phase contrast and confocal laser scanning microscopy. Besides the acquisition of SECM images, the UME was used to selectively attack a single living cell within the monolayer ensemble. Hydroxide ions were locally generated in the vicinity of a single target cell by the UME. The increase in pH induced cell necrosis that was subsequently imaged by SECM. It could be clearly demonstrated that the single target cell was selectively affected, whereas the adjacent reference cells remained unchanged.

Recent advances in high resolution scanning electrochemical microscopy of living cells--a review.

This review discusses advances in the field of high resolution scanning electrochemical microscopy (HR-SECM) and scanning ion conductance microscopy (SICM) to study living cells. Relevant references from the advent of this technique in the late 1980s to most recent contributions in 2012 are presented with special discussion on high resolution images. A clear progress especially within the last 5 years can be seen in the field of HR-SECM. Furthermore, we also concentrate on the intrinsic properties of SECM imaging techniques e.g. different modes of image acquisition, their advantages and disadvantages in imaging living cells and strategies for further enhancement of image resolution, etc. Some of the recent advances of SECM in nanoimaging have also been discussed which may have potential applications in high resolution imaging of cellular processes.