Acyl chain-dependent effect of lysophosphatidylcholine on endothelial prostacyclin production.

Previously we identified palmitoyl-lysophosphatidylcholine (16:0 LPC), linoleoyl-LPC (18:2 LPC), arachidonoyl-LPC (20:4 LPC), and oleoyl-LPC (18:1 LPC) as the most prominent LPC species generated by the action of endothelial lipase (EL) on high-density lipoprotein. In the present study, the impact of those LPC on prostacyclin (PGI(2)) production was examined in vitro in primary human aortic endothelial cells (HAEC) and in vivo in mice. Although 18:2 LPC was inactive, 16:0, 18:1, and 20:4 LPC induced PGI(2) production in HAEC by 1.

Robust extraction of functional signals from gene set analysis using a generalized threshold free scoring function.

Background: A central task in contemporary biosciences is the identification of biological processes showing response in genome-wide differential gene expression experiments. Two types of analysis are common. Either, one generates an ordered list based on the differential expression values of the probed genes and examines the tail areas of the list for over-representation of various functional classes.

Genetic similarity of chromosome 6 between patients receiving hematopoietic stem cell transplantation and HLA matched sibling donors.

Background: Matching for HLA genes located on chromosome 6 is required in hematopoietic stem cell transplantation to reduce the incidence of graft-versus-host disease. However, a considerable proportion of patients still suffer from it, obviously due to genetic differences outside the HLA gene region.

Design And Methods: We studied the similarity of almost 4,000 single nucleotide polymorphisms on chromosome 6 between patients receiving hematopoietic stem cell transplantation and their HLA-matched sibling donors.

Interspliced transcription chimeras: neglected pathological mechanism infiltrating gene accession queries?

Over half of the DNA of mammalian genomes is transcribed, and one of the emerging enigmas in the field of RNA research is intergenic splicing or transcription induced chimerism. We argue that fused low-copy-number transcripts constitute neglected pathological mechanism akin to copy number variation, due to loss of stoichiometric subunit ratios in protein complexes. An obstacle for transcriptomics meta-analysis of published microarrays is the traditional nomenclature of merged transcript neighbors under same accession codes.

Identification of alpha-1 acid glycoprotein as a lysophospholipid binding protein: a complementary role to albumin in the scavenging of lysophosphatidylcholine.

Alpha-1 acid glycoprotein (AGP, orosomucoid), a major acute phase protein in plasma, displays potent cytoprotective and anti-inflammatory activities whose molecular mechanisms are largely unknown. Because AGP binds various exogenous drugs, we have searched for endogenous ligands for AGP. We found that AGP binds lysophospholipids in a manner discernible from albumin in several ways.

The two ADF-H domains of twinfilin play functionally distinct roles in interactions with actin monomers.

Twinfilin is a ubiquitous and abundant actin monomer-binding protein that is composed of two ADF-H domains. To elucidate the role of twinfilin in actin dynamics, we examined the interactions of mouse twinfilin and its isolated ADF-H domains with G-actin. Wild-type twinfilin binds ADP-G-actin with higher affinity (K(D) = 0.

Structural conservation between the actin monomer-binding sites of twinfilin and actin-depolymerizing factor (ADF)/cofilin.

Twinfilin is an evolutionarily conserved actin monomer-binding protein that regulates cytoskeletal dynamics in organisms from yeast to mammals. It is composed of two actin-depolymerization factor homology (ADF-H) domains that show approximately 20% sequence identity to ADF/cofilin proteins. In contrast to ADF/cofilins, which bind both G-actin and F-actin and promote filament depolymerization, twinfilin interacts only with G-actin.

The three mouse actin-depolymerizing factor/cofilins evolved to fulfill cell-type-specific requirements for actin dynamics.

Actin-depolymerizing factor (ADF)/cofilins are essential regulators of actin filament turnover. Several ADF/cofilin isoforms are found in multicellular organisms, but their biological differences have remained unclear. Herein, we show that three ADF/cofilins exist in mouse and most likely in all other mammalian species.