The serini reaction

Zusammenfassung Der Mechanismus der Serini-Reaktion wird kurz erörtert und ein 17, 20-Oxyd als Zwischenprodukt vorgeschlagen. Das stereochemische Ergebnis der Reaktion soll von zwei Faktoren abhängig sein, und zwar: 1. von der Geometrie des « transition state » und 2. von der Konfiguration des Oxydrings. Ausgehend von diesen Überlegungen, kann vorausgesagt werden, daßReichsteins Substanz 0-Diacetat durch die Serini-Reaktion in ein 17-Iso-20-keton und nicht in ein 17-Normal-20-keton umgewandelt werden soll. Tatsächlich ist das 17-Isoallopregnanol-(3)-on-20 als einziges Produkt experimentell aufgefunden worden.     

A genome-wide association study for celiac disease identifies risk variants in the region harboring IL2 and IL21

We tested 310,605 SNPs for association in 778 individuals with celiac disease and 1,422 controls. Outside the HLA region, the most significant finding (rs13119723; P = 2.0 x 10(-7)) was in the KIAA1109-TENR-IL2-IL21 linkage disequilibrium block. We independently confirmed association in two further collections (strongest association at rs6822844, 24 kb 5' of IL21; meta-analysis P = 1.3 x 10(-14), odds ratio = 0.63), suggesting that genetic variation in this region predisposes to celiac disease.     

The human genome and understanding of common disease: present and future technologies

The study of candidate genes over the past three decades has yielded notable successes in common-disease genetics. During this time, however, interpretation of genetic association studies has been hampered by the use of clinical cohorts of inadequate power and insufficient information on genetic variation in candidate genes. The unavailability of highthroughput and low-cost genotyping technologies has also limited the scope of complex-disease genetic studies. More recently, however, the sequencing and characterization of variation within the human genome has revolutionized genetic studies and enabled full genome-wide scans for genes associated with disease. The identification of disease-associated (causative) genes has illuminated disease mechanisms. The translation of this knowledge into direct clinical benefit in diagnosis, prognosis and therapy for an individual’s disease still remains a challenge. Received 11 September 2006; received after revision 17 December 2006; accepted 18 January 2007     

Genetic studies of diseases

Genomic alterations lead to cancer complexity and form a major hurdle for comprehensive understanding of the molecular mechanisms underlying oncogenesis. In this review, we describe recent advances in studying cancer-associated genes from a systems biology point of view. The integration of known cancer genes onto protein and signaling networks reveals the characteristics of cancer genes within networks. This approach shows that cancer genes often function as network hub proteins which are involved in many cellular processes and form focal nodes in information exchange between many signaling pathways. Literature mining allows constructing gene-gene networks, in which new cancer genes can be identified. The gene expression profiles of cancer cells are used for reconstructing gene regulatory networks. By doing so, genes which are involved in the regulation of cancer progression can be picked up from these networks, after which their functions can be further confirmed in the laboratory.     

Genetic studies of diseases

Pancreatitis is usually inflammation of the pancreas without infection. Our understanding of pancreatitis has been built on autopsy studies, surgical biopsies and surrogate markers of inflammation and fibroses, including abdominal imaging techniques and pancreatic functional studies. However, the discovery that a number of different environmental factors and various genetic abnormalities are seen in patients with similar appearing pancreatitis phenotypes teaches us that end-stage pathology is not the disorder. Understanding complex associations and interactions requires that the components and their interactions be organized, stratified and functionally defined. Systems biology, in the broad sense, provides the approach and tools to define the complex mechanisms driving pathology. As the mathematics behind these pathways and mechanisms are defined and calibrated, the potential pathology of patients with early signs of disease can be predicted, and a number of patient-specific targets for intervention can be defined.     

Cellular internalization of proinsulin C-peptide

Proinsulin C-peptide is known to bind specifically to cell membranes and to exert intracellular effects, but whether it is internalized in target cells is unknown. In this study, using confocal microscopy and immunostained or rhodamine-labeled peptide, we show that C-peptide is internalized and localized to the cytosol of Swiss 3T3 and HEK-293 cells. In addition, transport into nuclei was found using the labeled peptide. The internalization was followed at 37°C for up to 1 h, and was reduced at 4°C and after preincubation with pertussis toxin. Hence, it is concluded to occur via an energy-dependent, pertussis toxin-sensitive mechanism and without detectable degradation within the experimental time course. Surface plasmon resonance measurements demonstrated binding of HEK-293 cell extract components to C-peptide, and subsequent elution of bound material revealed the components to be intracellular proteins. The identification of C-peptide cellular internalization, intracellular binding proteins, absence of rapid subsequent C-peptide degradation and apparent nuclear internalization support a maintained activity similar to that of an intracrine peptide hormone. Hence, the data suggest the possibility of one further C-peptide site of action. Received 31 October 2006; received after revision 27 December 2006; accepted 30 December 2006     

Polarized Emission of Molecular Film With Lanthanide (Ⅲ) Complex

1 Results In the coordination system by using complexation with organic ligand, the ff emission of lanthanide(Ⅲ) (Ln(Ⅲ)) is induced the excitation energy transfer form the organic chromophore under the light-irradiation. However, there are not so much number of reports to discuss the energy relaxation mechanism in such complexes with Ln(Ⅲ). Recently, we succeeded firstly to estimate the rate constant of the energy transfer between the ligand and Ln(Ⅲ) in Pr(Ⅲ)-phenanthroline analogs[1]. Here, we will di...