After 16 weeks, adalimumab demonstrated significantly superior efficacy and more rapid improvements in psoriasis compared with either methotrexate or placebo.

Pineal gland hormone melatonin binds and activates an orphan of the nuclear receptor superfamily.Michael Becker-André , Irmgard Wiesenberg, Nicole Schaeren-Wiemers, Elisabeth André , Martin Missbach, Jean-Hilaire Saurat, and Carsten Carlberg Correction submitted by Drs. Becker-André , SchaerenWiemers, and André:The article reported the identification of the pineal gland hormone melatonin as a natural ligand of the nuclear orphan receptor RZR␤. The article described transient transfection assays showing stimulation of RZR␤ transactivation by melatonin and in vitro binding studies showing a direct interaction between RZR␤ and melatonin. We were, however, not able to reproduce any of these experiments nor could we determine the reason for this failure. As the central finding of the article is based on these assays, we do not consider the drawn conclusions valid. All other data in the publication including our studies to localize RZR␤ mRNA using in situ hybridization and quantitative PCR are as published. We apologize to all investigators who have spent time and effort to reproduce parts of the work using the in vitro assays described in the article.Addition submitted by Drs. Wiesenberg, Missbach, Saurat, and Carlberg: RZR␤ belongs to the RZR/ROR family of nuclear receptors (1), where the members of this family have been shown to act as ligand-independent transcription factors that bind to monomeric binding sites mediating a high constitutive transcriptional activity (2-5). Recently, Greiner et al. (6) reported failure in observing transcriptional activity of RZR␤ on monomeric sites and its modulation by melatonin. However, in some cell lines, e.g. Drosophila SL-3 cells, the constitutive activity of RZR␤ and RZR/ROR␣ can clearly be reduced, e.g. by the omission of serum to the cell culture medium (2,7,8). Under these restricted experimental conditions RZR␤ and RZR/ROR␣ reproducibly function as ligand-dependent nuclear receptors (7-10). Ligand binding assays have been performed with cells overexpressing RZR/ROR and in vitro translated RZR/ROR (7, 8), but not with the purified receptor. This suggests but does not prove that melatonin is a ligand of RZR/ROR. However, the first report of a melatonin response element in the promoter of the human 5-lipoxygenase gene (11) has demonstrated an essential role of RZR/ROR as a mediator of nuclear melatonin signaling.

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