Novel synthesis and RNA-binding properties of aminoglycoside dimers conjugated via a naphthalene diimide-based intercalator.

The synthesis and RNA-binding properties of naphthalene-based diimide conjugated bis-aminoglycoside antibiotics are reported. Compared to the monomeric aminoglycoside, the conjugated ligands were observed to attain up to 35-fold enhancement in binding affinity towards a novel RNA construct that contained two 16S rRNA A-sites.

Different immune patterns in melancholic and non-melancholic major depression.

The search for immune patterns in major depression has thus far resulted in ambiguous findings, probably because patient samples are psychiatrically heterogeneous. We therefore focused on a detailed classification of subtypes of major depression, comparing patients with melancholic and non-melancholic major depression. Inpatients suffering from acute major depression were diagnosed and subclassified according to DSM IV criteria. Cell counts were determined by FACS analysis and morphology. Cytokine production (IL-2, IFN-gamma, IL-10) upon mitogen stimulation was measured by ELISA in a whole blood assay. Non-melancholic patients showed increased counts of leukocytes, lymphocytes and NK-cells in the acute stage of disease and after two and four weeks of treatment. Their lymphokine production was unchanged compared to that of healthy controls. Melancholic patients on the other hand demonstrated normal cell counts but a decreased production of IL-2, IFN-gamma and IL-10 during the acute stage of disease followed by a normalization with clinical improvement. Melancholic and non-melancholic patients showed different immune patterns. Classifying melancholic and non-melancholic patients is helpful towards the identification of immune characteristics typical for these diseases.

Inflammatory markers in major depression and melancholia.

BACKGROUND: There is evidence that patients with major depression (MD) also suffer an inflammatory immune reaction. However, the results remain ambiguous. This could be due to the psychiatrically heterogeneous patient samples investigated in many published studies. Since melancholic depression is psychopathologically and possibly etiologically different from non-melancholic MD, we focused on investigating immune parameters in these two subgroups. METHODS: 43 in-patients suffering from acute major depression were diagnosed, sub-classified according to DSM IV criteria, and compared to 43 matched healthy controls. Cell counts were determined by morphology, and acute phase proteins [c-reactive protein (CRP), alpha(2)-macroglobulin (A2M), haptoglobin (HP)] were measured by laser nephelometry. Cytokine production (IL-1beta) upon mitogen stimulation was measured by ELISA in a whole blood assay. RESULTS: Non-melancholic patients showed increased monocyte counts and A2M serum concentrations in the acute stage of disease and after 2 and 4 weeks of treatment. Melancholic patients demonstrated a decreased monocyte count upon admission and after 4 weeks of treatment. HP levels and IL-1beta production were unchanged in all studied subjects. LIMITATIONS: Medication of the patients varied. The differentiation between melancholic and non-melancholic depression was performed clinically and was not performed using any standardized instrument. CONCLUSION: Melancholic and non-melancholic patients show different immune patterns. This differentiation might clarify immunological findings in MD and point towards etiological factors that are involved in the development of various subtypes of MD.

Binding of a cyclic BIV beta-Tat peptide with its TAR RNA construct.

The ability of RNA structures to adopt diverse yet complex tertiary structures has resulted in numerous fascinating RNA-protein recognition events. It was recently reported that a close relative of the HIV Rev peptide, namely a 17 residue Tat peptide from bovine immuno-deficiency virus (BIV), is able to bind to the 28 nucleotide BIV TAR RNA construct. Here we report that by simply converting the 17 residue beta-ribbon peptide structure to a 19 residue cyclopeptide, the binding affinity (Kd) of the resulting cyclopeptide to the TAR RNA target, observed by fluorescence binding study, was enhanced approximately 5-fold.