Fragments of SLIT3 inhibit cellular migration.

The repellent factor family of Slit molecules has been described as having a repulsive function in the developing nervous system on growing axons expressing the Roundabout (Robo) receptors. Recent studies determined the effects of Slit molecules on the migratory and invasive potential of several types of tumor cells but also on synovial fibroblasts (SFs) derived from rheumatoid arthritis (RA) patients. To optimize a potential therapeutic application we aimed at generatingfragments of Slit3 showing the same functional ability as the full-length molecule but having the advantage of a smaller size.

GDF-5 and BMP-2 regulate bone cell differentiation by gene expression of MSX1, MSX2, Dlx5, and Runx2 and influence OCN gene expression in vitro.

Recombinant human growth/differentiation factor 5 (rhGDF-5) and recombinant human bone morphogenetic protein 2 (rhBMP-2), as members of the transforming growth factor Β family, influence bone formation and differentiation. This in vitro osteoblast cell culture study investigated the molecular biologic effect of these growth factors on regulator gene expression of the homebox proteins MSX1 and MSX2 as well as distal-less homebox 5 (Dlx5) and runt-related transcription factor 2 (Runx2/Cbfa1). Concerning effector genes, the messenger ribonucleic acids of osteocalcin (OCN) were quantified using a reverse transcriptase real-time polymerase chain reaction.

Lack of the mesodermal homeodomain protein MEOX1 disrupts sclerotome polarity and leads to a remodeling of the cranio-cervical joints of the axial skeleton.

Meox1 and Meox2 are two related homeodomain transcription factor genes that together are essential for the development of all somite compartments. Here we show that mice homozygous for Meox1 mutations alone have abnormalities that are restricted to the sclerotome and its derivatives. A prominent and consistent phenotype of these mutations is a remodeling of the cranio-cervical joints whose major feature is the assimilation of the atlas into the basioccipital bone so that the skull rests on the axis.

A natural variant of the heme-binding signature (R441C) resulting in complete loss of function of CYP2D6.

A new variant allele CYP2D6*62 (g.4044C>T; R441C) of the drug-metabolizing cytochrome P450 (P450) CYP2D6 was identified in a person with reduced sparteine oxidation phenotype, which was unexpected based on a genetic CYP2D6*1A/*41 background. The recombinantly expressed variant protein had no activity toward propafenone as a result of missing heme incorporation.

Increased levels of aflatoxin-albumin adducts are associated with CYP3A5 polymorphisms in The Gambia, West Africa.

Objectives: Major risk factors for hepatocellular carcinoma (HCC) are hepatitis viruses and exposure to aflatoxins, including aflatoxin B1 (AFB1). The mutagenic effect of AFB1 results from hepatic bioactivation to AFB1-exo-8,9-epoxide. This is in part catalysed by CYP3A5, an enzyme expressed polymorphically.