External Fields as a Probe for Fundamental Physics

Quantum vacuum experiments are becoming a flexible tool for investigating fundamental physics. They are particularly powerful for searching for new light but weakly interacting degrees of freedom and are thus complementary to accelerator-driven experiments. I review recent developments in this field, focusing on optical experiments in strong electromagnetic fields. In order to characterize potential optical signatures, I discuss various low-energy effective actions which parameterize the interaction of particle-physics candidates with optical photons and external electromagnetic fields. Experiments with an electromagnetized quantum vacuum and optical probes do not only have the potential to collect evidence for new physics, but special-purpose setups can also distinguish between different particle-physics scenarios and extract information about underlying microscopic properties.Comment: 12 pages, plenary talk at QFEXT07, Leipzig, September 200

Periostin is up-regulated in high grade and high stage prostate cancer

BACKGROUND: Expression of periostin is an indicator of epithelial-mesenchymal transition in cancer but a detailed analysis of periostin expression in prostate cancer has not been conducted so far. METHODS: Here, we evaluated periostin expression in prostate cancer cells and peritumoural stroma immunohistochemically in two independent prostate cancer cohorts, including a training cohort (n = 93) and a test cohort (n = 325). Metastatic prostate cancers (n = 20), hormone refractory prostate cancers (n = 19) and benign prostatic tissues (n = 38) were also analyzed. RESULTS: In total, strong epithelial periostin expression was detectable in 142 of 418 (34.0%) of prostate carcinomas and in 11 of 38 benign prostate glands (28.9%). Increased periostin expression in carcinoma cells was significantly associated with high Gleason score (p < 0.01) and advanced tumour stage (p < 0.05) in the test cohort. Whereas periostin expression was weak or absent in the stroma around normal prostate glands, strong periostin expression in tumour stroma was found in most primary and metastatic prostate cancers. High stromal periostin expression was associated with higher Gleason scores (p < 0.001). There was a relationship between stromal periostin expression and shortened PSA relapse free survival times in the training cohort (p < 0.05). CONCLUSIONS: Our data indicate that periostin up-regulation is related to increased tumour aggressiveness in prostate cancer and might be a promising target for therapeutical interventions in primary and metastatic prostate cancer

Structural aspects of recently discovered viral deubiquitinating activities

Protein ubiquitination has been identified as a regulatory mechanism in key cellular activities, and deubiquitination is recognized as an important step in processes governed by ubiquitin and ubiquitin-like modifiers. Viruses are known to target ubiquitin and ubiquitin-like modifier pathways using various strategies, including the recruitment of host deubiquitinating enzymes. Deubiquitinating activities have recently been described for proteins from three different virus families (adenovirus, coronavirus and herpesvirus), and predicted for others. This review centers on structural-functional aspects that characterize the confirmed viral deubiquitinating enzymes, and their relationships to established families of cellular deubiquitinating enzymesNRC publication: Ye

Probing the acyl-binding pocket of aminoacylase-1

The aminoacylase-1/metallopeptidase 20 (Acy1/M20) family features several l-aminoacylases useful in biocatalysis. Mammalian Acy1, in particular, has been applied in racemic resolution and reverse hydrolysis. Despite recent advances in our understanding of the active site architecture and functioning, determinants of Acy1 substrate specificity have remained uncharted. Comparison to bacterial homologues points to a sterically more restricted acyl-binding pocket for Acy1. Here we sought to map characteristics of the acyl-binding pocket of human and porcine Acy1. Toward this end, we determined Michaelis constants for an analogue series of aliphatic N-acyl- l-methionine substrates and translated the values into three-dimensional quantitative structure-activity relationship models employing the minimal topological difference-partial least square method. The QSAR models for the two enzymes suggest overall similar binding pockets in the acetyl-binding portion and indicate a general preference for straight-chain acyl moieties. Embedding of the QSAR map for human Acy1 in the structure of its metal-binding domain associates the side chain of Ile177 with limited acyl chain elongation which was not observed for the porcine enzyme. The topological model further supports roles of Thr347 and Leu372, which are both conserved in the porcine enzyme, in restricting acyl chain branching at the alpha- and beta-positions, respectively. Mutational analyses confirmed our predictions for Thr347 and Leu372. Moreover, the T347S variant of human Acy1 exhibited markedly increased catalytic efficiency against N-benzoylamino acids, demonstrating the potential for engineering of substrate specificity in Acy1. We discuss the more general application of the employed procedure for protein designNRC publication: Ye

Probing the acyl-binding pocket of aminoacylase-1

The aminoacylase-1/metallopeptidase 20 (Acy1/M20) family features several l-aminoacylases useful in biocatalysis. Mammalian Acy1, in particular, has been applied in racemic resolution and reverse hydrolysis. Despite recent advances in our understanding of the active site architecture and functioning, determinants of Acy1 substrate specificity have remained uncharted. Comparison to bacterial homologues points to a sterically more restricted acyl-binding pocket for Acy1. Here we sought to map characteristics of the acyl-binding pocket of human and porcine Acy1. Toward this end, we determined Michaelis constants for an analogue series of aliphatic N-acyl- l-methionine substrates and translated the values into three-dimensional quantitative structure-activity relationship models employing the minimal topological difference-partial least square method. The QSAR models for the two enzymes suggest overall similar binding pockets in the acetyl-binding portion and indicate a general preference for straight-chain acyl moieties. Embedding of the QSAR map for human Acy1 in the structure of its metal-binding domain associates the side chain of Ile177 with limited acyl chain elongation which was not observed for the porcine enzyme. The topological model further supports roles of Thr347 and Leu372, which are both conserved in the porcine enzyme, in restricting acyl chain branching at the alpha- and beta-positions, respectively. Mutational analyses confirmed our predictions for Thr347 and Leu372. Moreover, the T347S variant of human Acy1 exhibited markedly increased catalytic efficiency against N-benzoylamino acids, demonstrating the potential for engineering of substrate specificity in Acy1. We discuss the more general application of the employed procedure for protein designNRC publication: Ye