Molecular Identification and Expression Analysis of Filaggrin-2, a Member of the S100 Fused-Type Protein Family

Genes of the S100 fused-type protein (SFTP) family are clustered within the epidermal differentiation complex and encode essential components that maintain epithelial homeostasis and barrier functions. Recent genetic studies have shown that mutations within the gene encoding the SFTP filaggrin cause ichthyosis vulgaris and are major predisposing factors for atopic dermatitis. As a vital component of healthy skin, filaggrin is also a precursor of natural moisturizing factors. Here we present the discovery of a member of this family, designated as filaggrin-2 (FLG2) that is expressed in human skin. The FLG2 gene encodes a histidine- and glutamine-rich protein of approximately 248 kDa, which shares common structural features with other SFTP members, in particular filaggrin. We found that FLG2 transcripts are present in skin, thymus, tonsils, stomach, testis and placenta. In cultured primary keratinocytes, FLG2 mRNA expression displayed almost the same kinetics as that of filaggrin following Ca2+ stimulation, suggesting an important role in molecular regulation of epidermal terminal differentiation. We provide evidences that like filaggrin, FLG2 is initially expressed by upper granular cells, proteolytically processed and deposited in the stratum granulosum and stratum corneum (SC) layers of normal epidermis. Thus, FLG2 and filaggrin may have overlapping and perhaps synergistic roles in the formation of the epidermal barrier, protecting the skin from environmental insults and the escape of moisture by offering precursors of natural moisturizing factors

Pre-Packed Vacuum Bone Cement Mixing Systems. A Further Step in Reducing Methylmethacrylate Exposure in Surgery

Methods: A pre-packed vacuum mixing system (Optipac (R)) was compared with two standard systems (Palamix (R) and Easymix (R)) regarding MMA emission. The latter systems require loading with the bone cement compounds prior to mixing. Following a standardized procedure, 10 mixes were performed with each system and the emission of MMA vapours in the breathing zone was recorded using photoionization detection over a period of 3 min. Results: The mean MMA exposure was reduced when using the pre-packed system compared to the devices that require filling with the components. The highest emission peaks were recorded during the mixing and preparation steps in all systems. Conclusions: Modern pre-packed vacuum mixing systems further help to reduce the occupational hazards created by bone cement preparation. However, MMA fumes can still be detected using this technique. Although this is an important step in reducing MMA exposure in the operating theatre, further technical effort has to be taken to eliminate the continuous leakage of monomer from the devices while mixing and to minimize necessary manipulation for final delivery

Functional midterm outcome in 131 consecutive cases of surgical clubfoot treatment

Since introduction and widespread use of the Ponseti method in the last decade, the need for surgical treatment of clubfeet is nowadays limited to resistant cases. In the time before, surgery via dorsomedial release was a very common treatment option. Very few long-term follow-up studies cover the outcome of surgical methods, which is particularly interesting, as clinical results rather worsen with time. In the present study, 98 children (131 clubfeet), who underwent surgical correction using the Imhauser method at the age of 4.5 months were included. Follow-up time was 8.2 years (0-11.8 years) at average. Data could be retrieved from 46 patients (71 feet), only 5 patients (7 feet) were lost to follow-up. The rate of relapses was high, as 47 patients (53 feet) needed surgical revision for recurrence, while clinical scores showed a good result in the Laaveg and Ponseti Score and the Foot-Function-Index. Isokinetic testing and clinical data indicated a significant weakness of the treated foot, when compared to the healthy side in 12 patients with unilateral deformity. The presented study supports like others the issue that the clinical outcome of a surgical, posteromedial release in terms of relapses is disappointing. This fact is apparently not sufficiently reflected in the current clinical scores, which showed rather good results. As the question of evaluation methods for results of clubfoot treatment remains controversial, isokinetic testing is an easy to use alternative that provides detailed information about functional limitations and may help in reducing the need for repeated radiographic examinations

Constitutive formation of caveolae in a bacterium

Caveolin plays an essential role in the formation of characteristic surface pits, caveolae, which cover the surface of many animal cells. The fundamental principles of caveola formation are only slowly emerging. Here we show that caveolin expression in a prokaryotic host lacking any intracellular membrane system drives the formation of cytoplasmic vesicles containing polymeric caveolin. Vesicle formation is induced by expression of wild-type caveolins, but not caveolin mutants defective in caveola formation in mammalian systems. In addition, cryo-electron tomography shows that the induced membrane domains are equivalent in size and caveolin density to native caveolae and reveals a possible polyhedral arrangement of caveolin oligomers. The caveolin-induced vesicles or heterologous caveolae (h-caveolae) form by budding in from the cytoplasmic membrane, generating a membrane domain with distinct lipid composition. Periplasmic solutes are encapsulated in the budding h-caveola, and purified h-caveolae can be tailored to be targeted to specific cells of interest