With the newer generations of multidetector CT scanners, the diagnostic performance for the assessment of coronary artery disease has significantly improved, and the proportion of nonassessable segments has decreased.

On MSCT, differences in plaque characterization were demonstrated between patients with ACS and stable CAD. Plaques of ACS patients showed features of vulnerability to rupture on VH IVUS. Potentially, MSCT may be useful for non-invasive identification of atherosclerotic plaque patterns associated with higher risk.

The Armadillo protein p120 ctn associates with the cytoplasmic domain of cadherins and accumulates at cell-cell junctions. Particular Armadillo proteins such as ␤-catenin and plakophilins show a partly nuclear location, suggesting gene-regulatory activities. For different human E-cadherin-negative carcinoma cancer cell lines we found expression of endogenous p120 ctn in the nucleus. Expression of E-cadherin directed p120 ctn out of the nucleus. Previously, we reported that the human p120 ctn gene might encode up to 32 protein isoforms as products of alternative splicing. Overexpression of p120 ctn isoforms B in various cell lines resulted in cytoplasmic immunopositivity but never in nuclear staining. In contrast, upon expression of p120 ctn cDNAs lacking exon B, the isoforms were detectable within both nuclei and cytoplasm. A putative nuclear export signal (NES) with a characteristic leucine-rich motif is encoded by exon B. This sequence element was shown to be required for nuclear export and to function autonomously when fused to a carrier protein and microinjected into cell nuclei. Moreover, the NES function of endogenously or exogenously expressed p120 ctn isoforms B was sensitive to the nuclear export inhibitor leptomycin B. Expression of exogenous E-cadherin down-regulated nuclear p120 ctn whereas activation of protein kinase C increased the level of nuclear p120 ctn . These results reveal molecular mechanisms controlling the subcellular distribution of p120 ctn .

Pharmacological and genetic tools targeting the 5-hydroxytryptamine (5-HT)7 receptor in preclinical animal models have implicated this receptor in diverse (patho)physiological processes of the central nervous system (CNS). Some data obtained with 5-HT7 receptor knockout mice, selective antagonists, and, to a lesser extent, agonists, however, are quite contradictory. In this review, we not only discuss in detail the role of the 5-HT7 receptor in the CNS but also propose some hypothetical models, which could explain the observed inconsistencies. These models are based on two novel concepts within the field of G protein-coupled receptors (GPCR), namely biphasic signaling and G protein-independent signaling, which both have been shown to be mediated by GPCR dimerization. This led us to suggest that the 5-HT7 receptor could reside in different dimeric contexts and initiate different signaling pathways, depending on the neuronal circuitry and/or brain region. In conclusion, we highlight GPCR dimerization and G protein-independent signaling as two promising future directions in 5-HT7 receptor research, which ultimately might lead to the development of more efficient dimer- and/or pathway-specific therapeutics.

No abstract

An important reason for preferring mammalian cells for heterologous gene expression is their ability to make authentic proteins containing post-translational modifications similar to those of the native protein. The development of expression systems for mammalian cells has been ongoing for several years, resulting in a wide variety of effective expression vectors. The aim of this review is to highlight episomal expression vectors. Such episomal plasmids are usually based on sequences from DNA viruses, such as BK virus, bovine papilloma virus 1 and Epstein±Barr virus. In this review we will mainly focus on the improvements made towards the usefulness of these systems for gene expression studies and gene therapy.

A good correlation was observed between calcium quantification on MSCT and VH IVUS. In addition, plaque classification on MSCT paralleled relative plaque composition on VH IVUS, although VH IVUS provided more precise plaque characterization. Mixed plaques on MSCT were associated with high-risk features on VH IVUS.

Like most neurotransmitters, serotonin possesses a simple structure. However, the pharmacological consequences are more complex and diverse. Serotonin is involved in numerous functions in the human body including the control of appetite, sleep, memory and learning, temperature regulation, mood, behavior, cardiovascular function, muscle contraction, endocrine regulation, and depression. Low levels of serotonin may be associated with several disorders, namely increase in aggressive and angry behaviors, clinical depression, Parkinson's disease, obsessive-compulsive disorder, eating disorders, migraine, irritable bowel syndrome, tinnitus, and bipolar disease. These effects are mediated via different serotonin (5-HT) receptors. In this review, we will focus on the last discovered member of this serotonin receptor family, the 5-HT7 receptor. This receptor belongs to the G protein-coupled receptor superfamily and was cloned two decades ago. Later, different splice variants were described but no major functional differences have been described so far. All 5-HT7 receptor variants are coupled to Gαs proteins and stimulate cAMP formation. Recently, several interacting proteins have been reported, which can influence receptor signaling and trafficking.