Identification and relative quantification of neuropeptides from the endocrine tissues.

Endocrine tissues like the pituitary, hypothalamus and islets of Langerhans are rich in bioactive peptides. These are used for intercellular signalling and are involved in regulation of almost all physiological processes. Peptidomics is the comprehensive analysis of peptides in tissues, fluids and cells.

Sensory deficits in mice hypomorphic for a mammalian homologue of unc-53.

The migration of cells and the extension of cellular processes along pathways to their defined destinations are crucial in the development of higher organisms. Caenorhabditis elegans unc-53 plays an important role in cell migration and the outgrowth of cellular processes such as axons. To gain further insight into the biological function of unc53H2, a recently identified mammalian homologue of unc-53, we have generated mice carrying a mutation of unc53H2 and provide evidence that unc53H2 is involved in neuronal development and, more specifically, the development of different sensory systems.

Functional study of rat 5-HT2A receptors using antisense oligonucleotides.

We studied the effects in rats of a 6-day intracerebroventricular (i.c.v) infusion of four different end-capped phosphorothioate-modified antisense oligonucleotides (AOs), specifically targeting different regions of the 5-hydroxytryptamine2A (5-HT2A) receptor mRNA, on central 5-HT2A receptor expression and 5-HT2A receptor-mediated behaviours.

Ten years of antisense inhibition of brain G-protein-coupled receptor function.

Antisense oligonucleotides (AOs) are widely used as tools for inhibiting gene expression in the mammalian central nervous system. Successful gene suppression has been reported for different targets such as neurotransmitter receptors, neuropeptides, ion channels, trophic factors, cytokines, transporters, and others. This illustrates their potential for studying the expression and function of a wide range of proteins.

Gene-Expression - Based Responses to Drug Treatment.

Perfect drugs are potent, specific and nontoxic. Many compounds fail because of unexpected toxicity and lack of efficacy in later stages of clinical development. Therefore, more complete knowledge and understanding of the properties of a drug is needed at an earlier stage of drug development.

5-HT2A and 5-HT2C receptors and their atypical regulation properties.

The 5-HT(2A) and 5-HT(2C) receptors belong to the G-protein-coupled receptor (GPCR) superfamily. GPCRs transduce extracellular signals to the interior of cells through their interaction with G-proteins. The 5-HT(2A) and 5-HT(2C) receptors mediate effects of a large variety of compounds affecting depression, schizophrenia, anxiety, hallucinations, dysthymia, sleep patterns, feeding behaviour and neuro-endocrine functions.

Functional genomics approaches for the identification and validation of antifungal drug targets.

So far, antifungal drug discovery seems to have benefited little from the enormous advances in the field of genomics in the last decade. Although it has become clear that traditional drug screening is not delivering the long-awaited novel potent antifungals, little has been reported on efforts to use novel genome-based methodologies in the quest for new drugs acting on human pathogenic fungi. Although the market for a novel systemic and even topical broad-spectrum antifungal appears considerable, many large pharmaceutical companies have decided to scale back their activities in antifungal drug discovery.

Single allele knock-out of Candida albicans CGT1 leads to unexpected resistance to hygromycin B and elevated temperature.

Almost all eukaryotic mRNAs are capped at their 5'-terminus. Capping is crucial for stability, processing, nuclear export and efficient translation of mRNA. We studied the phenotypic effects elicited by depleting a Candida albicans strain of mRNA 5'-guanylyltransferase (mRNA capping enzyme; CGT1).