The c-terminus of GRK3 indicates rapid dissociation of G protein heterotrimers

Signals mediated by heterotrimeric G proteins often develop over the course of tens of milliseconds, and could require either conformational rearrangement or complete physical dissociation of Gαβγ heterotrimers. Although it is known that some active heterotrimers are dissociated (into Gα and Gβγ) at steady-state, it is not clear that dissociation occurs quickly enough to participate in rapid signaling. Here we show that fusion proteins containing the c-terminus of GPCR kinase 3 (GRK3ct) and either the fluorescent protein cerulean or Renilla luciferase bind to venus-labeled Gβγ dimers (Gβγ-V), resulting in Förster or bioluminescence resonance energy transfer (FRET or BRET). GRK3ct fusion proteins are freely-diffusible, and do not form preassembled complexes with G proteins. GRK3ct fusion proteins bind to free Gβγ-V dimers but not to rearranged heterotrimers, and thus can report G protein dissociation with high temporal resolution. We find that heterotrimer dissociation can occur in living cells in less than 100 ms. Under the conditions of these experiments diffusion and collision of masGRK3ct fusion proteins and Gβγ-V were not rate-limiting. These results indicate that G protein heterotrimers can dissociate quickly enough to participate in rapid signaling.     

Pollution control by wetlands

The 2nd International Symposium on Wetland Pollutant Dynamics and Control (WETPOL 2007), organised by the Department of Geography of the University of Tartu (Estonia) in co-operation with partners from the Estonian University of Life Sciences (Tartu, Estonia), Ghent University (Belgium), and the UNESCO-IHE (Delft, The Netherlands), was held 16–20 September 2007, in Tartu, Estonia. At this meeting, 140 oral presentations (including 9 keynote speeches) and 70 posters by representatives from 38 countries were presented. About half of the presentations considered purification processes in both semi-natural and constructed wetlands. The editorial paper highlights trends in studying the cycling of nitrogen, phosphorus, carbon, heavy metals, and organic pollutants in wetlands, but also in the modelling of pollutant removal and the functioning of plants in the wetland environment. It also describes the WETPOL 2007 meeting, which served as the source of the selected papers, and briefly explains the main aspects of these papers.     

Discovery and biological activity of computer-assisted drug designed Akt pathway inhibitors

The P13K/Akt pathway is a growth-regulating cellular signaling pathway that is over-activated in numerous human cancers. A novel series of Akt pathway inhibitors were identified using iterative pharmacophore modeling, energy-based calculations, and property predictions of known Akt inhibitors. Inhibitory effects on activation of Akt and growth of human neoplastic cells are reported. Results show variable inhibitory effects of three selected compounds on Akt phosphorylation at a key activation site, and on proliferation of tumorigenic cells. We identify one lead compound with potent inhibitory activity on both human carcinoma cell proliferation and Akt activation.     

Referate

Ohne Zusammenfassung     

Das genotypische Milieu in seiner Wirkung auf einige Glieder der dumpy-Allelen-Serie beiDrosophila melanogaster

Ohne ZusammenfassungMit 11 Textfiguren     

MR-proADM and MR-proANP levels in patients with acute pulmonary embolism

BackgroundThe aim of this study was to determine levels of Mid-regional Pro-adrenomedullin (MR-proADM) and Mid-regional Pro-atrial Natriuretic Peptide (MR-proANP) in patients with acute pulmonary embolism (PE), the relationship between these parameters and the risk classification in addition to determining the relationship between 1and 3month mortality.Methods82 PE patients and 50 healthy control subjects were included in the study. Blood samples for Mr-proANP and Mr-proADM were obtained from the subjects prior to the treatment. Risk stratification was determined according to sPESI (Simplified Pulmonary Embolism Severity Index). Following these initial measurements, cases with PE were assessed in terms of all causative and PE related mortalities.ResultsThe mean serum Mr-proANP and Mr-proADM levels in acute PE patients were found to be statistically higher compared to the control group (p < 0.001, p < 0.01; respectively) and statistically significantly higher in high-risk patients than low-risk patients (p < 0.01, p < 0.05; respectively). No statistical difference was determined in high-risk patients in case of sPESI compared to low-risk patients while hospital mortality rates were higher. It was determined that the hospital mortality rate in cases with Mr-proANP ≥ 123.30 pmol/L and the total 3-month mortality rate in cases with Mr-proADM ≥ 152.2 pg/mL showed a statistically significant increase.ConclusionsThis study showed that Mr-proANP and MRproADM may be an important biochemical marker for determining high-risk cases and predicting the mortality in PE patients and we believe that these results should be supported by further and extensive studies.     

Evaluation of the interaction between proliferation,oxidant–antioxidant status,Wnt pathway,and apoptosis in zebrafish embryos exposed to silver nanoparticles used in textile industry

Antimicrobial textile products are developing rapidly as an important part of functional textiles. Silver nanoparticles (AgNPs) are nanotechnology products with antimicrobial properties. However, exposure to nanoparticles in daily life is an important issue for public health, still being updated. Aim was to evaluate the effects of AgNPs on the development of zebrafish embryos focusing on Wnt pathway, proliferation, oxidant–antioxidant status, and apoptosis. The expressions of ccnd1 and gsk3β were determined by RT‐PCR, whereas β‐catenin and proliferative cell antigen (PCNA) expressions were determined immunohistochemically. Lipid peroxidation, superoxide dismutase, and glutathione‐S‐transferase activities were determined spectrophotometrically. Apoptosis was determined using acridine orange staining. Oxidant status, apoptosis, immunohistochemical PCNA, and β catenin staining increased, whereas ccnd1 and antioxidant enzyme activities decreased in AgNPs‐exposed embryos in a dose‐dependent manner. Our results indicate the interaction of possible mechanisms that may be responsible for the toxic effects of AgNPs in zebrafish embryos.