Efficient removal of black henna tattoos.

Background/objectives: Para-phenylenediamine, a dye frequently added to henna tattoos to create the black color, is a potent contact allergen. Severe contact dermatitis may arise within days even after the first application. Our objective was to develop a method for rapid and complete removal of para-phenylenediamine-containing black henna tattoos from the skin, an important problem many physicians are confronted with, but for which no simple method exists.

Hereditary angioedema in a single family with specific mutations in both plasminogen and SERPING1 genes.

Background: Hereditary angioedema (HAE) is a group of genetic diseases characterized by recurrent, painful and potentially lethal tissue swelling. The most common form results from mutations in the SERPING1 gene, leading to reduced function of complement 1 inhibitor (C1-INH). Rarer forms with normal C1-INH may arise from mutations in the coagulation factor F12 gene, but mostly the genetic background is unknown.

ERp29 deficiency affects sensitivity to apoptosis via impairment of the ATF6-CHOP pathway of stress response.

Endoplasmic reticulum protein 29 (ERp29) belongs to the redox-inactive PDI-Dβ-subfamily of PDI-proteins. ERp29 is expressed in all mammalian tissues examined. Especially high levels of expression were observed in secretory tissues and in some tumors.

Peptide binding by catalytic domains of the protein disulfide isomerase-related protein ERp46.

The protein disulfide isomerase (PDI) family member ERp46/endoPDI/thioredoxin domain-containing protein 5 is preferentially expressed in a limited number of tissues, where it may function as a survival factor for nitrosative stress in vivo. It is involved in insulin production as well as in adiponectin signaling and interacts specifically with the redox-regulatory endoplasmic reticulum proteins endoplasmic oxidoreductin 1α (Ero1α) and peroxiredoxin-4. Here, we show that ERp46, although lacking a PDI-like redox-inactive b'-thioredoxin domain with its hydrophobic substrate binding site, is able to bind to a large pool of peptides containing aromatic and basic residues via all three of its catalytic domains (a(0), a and a'), though the a(0) domain may contain the primary binding site.

Crystal structure and functional analysis of the protein disulfide isomerase-related protein ERp29.

The protein disulfide isomerase-related protein ERp29 is a putative chaperone involved in processing and secretion of secretory proteins. Until now, however, both the structure and the exact nature of interacting substrates remained unclear. We provide for the first time a crystal structure of human ERp29, refined to 2.

CD137 ligand reverse signaling has multiple functions in human dendritic cells during an adaptive immune response.

T cell activation via dendritic cells (DC) is an important step in the adaptive immune response, which requires DC maturation, migration to lymph nodes and presentation of antigen to T cells. CD137 receptor expressed on activated T cells is a potent costimulatory molecule. Here, we investigated the functions of CD137 ligand (CD137L) in human monocyte-derived DC during an immune response.

An essential role for Pin1 in Xenopus laevis embryonic development revealed by specific inhibitors.

The peptidyl prolyl cis/trans isomerase (PPIase) Pin1 plays an important role in phosphorylation-dependent events of the cell cycle. This function is linked to its display of two phosphothreonine/phosphoserine-proline binding motifs, one within the type IV WW domain and a second within the parvulin-like catalytic domain. By microinjection of the compound Ac-Phe-D-Thr(PO3H2)-Pip-Nal-Gln-NH2, which inhibits Xenopus laevis Pin1 with a Ki value of 19.

Endobrevin/VAMP8 mediates exocytotic release of hexosaminidase from rat basophilic leukaemia cells.

Mast cells are important players in innate immunity and mediate allergic responses. Upon stimulation, they release biologically active mediators including histamine, cytokines and lysosomal hydrolases. We used permeabilized rat basophilic leukaemia cells as model to identify R-SNAREs (soluble NSF (N-ethylmaleimide-sensitive fusion protein)) mediating exocytosis of hexosaminidase from mast cells.

Conserved structural and functional properties of D-domain containing redox-active and -inactive protein disulfide isomerase-related protein chaperones.

The structure and mode of binding of the endoplasmic reticulum protein disulfide isomerase-related proteins to their substrates is currently a focus of intensive research. We have recently determined the crystal structure of the Drosophila melanogaster protein disulfide isomerase-related protein Wind and have described two essential substrate binding sites within the protein, one within the thioredoxin b-domain and another within the C-terminal D-domain. Although a mammalian ortholog of Wind (ERp29/28) is known, conflicting interpretations of its structure and putative function have been postulated.

Structural elucidation of the PDI-related chaperone Wind with the help of mutants.

The structures of the PDI-related protein Wind (with a C-terminal His(6) tag) and the mutants Y53S, Y53F and Y55K have been determined and compared with the wild-type structure with the His(6) tag at the N-terminus. All five structures show the same mode of dimerization, showing that this was not an artefact introduced by the nearby N-terminal His(6) tag and suggesting that this dimer may also be the biologically active form. Although the mutants Y53S and Y55K completely abrogate transport of the protein Pipe (which appears to be the primary function of Wind in the cell), only subtle differences can be seen in the putative Pipe-binding region.

Mapping of a substrate binding site in the protein disulfide isomerase-related chaperone wind based on protein function and crystal structure.

The protein disulfide isomerase (PDI)-related protein Wind is essential in Drosophila melanogaster, and is required for correct targeting of Pipe, an essential Golgi transmembrane 2-O-sulfotransferase. Apart from a thioredoxin fold domain present in all PDI proteins, Wind also has a unique C-terminal D-domain found only in PDI-D proteins. Here, we show that Pipe processing requires dimeric Wind, which interacts directly with the soluble domain of Pipe in vitro, and we map an essential substrate binding site in Wind to the vicinity of an exposed cluster of tyrosines within the thioredoxin fold domain.

Crystal structure and functional analysis of Drosophila Wind, a protein-disulfide isomerase-related protein.

In the developing Drosophila melanogaster embryo, dorsal-ventral patterning displays an absolute requirement for the product of the essential windbeutel gene, Wind. In homozygous windbeutel mutant flies, dorsal-ventral patterning fails to initiate because of the failure of the Golgi-resident proteoglycan-modifying protein, Pipe, to exit the endoplasmic reticulum, and this leads to the death of the embryo. Here, we describe the three-dimensional structure of Wind at 1.