Regulation of mammalian CDC6 by CDK phosphorylation and proteasome dependent degradation.

The mammalian cell cycle is regulated by periodic gene transcription, kinase activities and protein degradation. A human cDNA encoding a protein homologous to S. cerevisiae Cdc6p and S. pombe Cdc18 was identified. Mammalian CDC6 is essential for DNA replication, and the obtained data demonstrate that the mammalian CDC6 protein is regulated by several mechanisms. The subcellular localization of mammalian CDC6 is cell cycle regulated controlled by Cyclin A/CDK2 phosphorylation. The CDC6 protein interacts directly with the Cyclin A/CDK2 complex via a Cy-motif in the N-terminal of CDC6 and phosphorylation of hCDC6 results in relocation of hCDC6 from the nucleus to the cytoplasm during S- phase. The protein level of mammalian CDC6 is growth and cell cycle regulated. The CDC6 protein is induced by stimulation of serum starved fibroblasts and the CDC6 protein level remains high throughout S-phase and G2. As cells progress through mitosis the amount of CDC6 protein declines abruptly. Mammalian CDC6 is an unstable protein. The level of CDC6 protein increases in the presence of proteasome inhibitors and, furthermore, poly-ubiquitinated CDC6 was identified in vivo, demonstrating that CDC6 is targeted for degradation by ubiquitination in mammalian cells. The instability of CDC6 was shown to be dependent on the N- terminal region. A peptide sequence with homology to destruction box sequences found in substrates of the anaphase promoting complex was identified in hCDC6 and shown to mediate the degradation of hCDC6 in quiescent cells. These data suggest that the mammalian CDC6 protein is highly regulated. In GO and early G1 accumulation of the mammalian CDC6 protein is prevented by ubiquitin mediated degradation. During S-phase and G2 mammalian CDC6 is retained in the cytoplasm by Cyclin A/CDK2 phosphorylation

Degraded Arabinogalactans and Their Binding Properties to Cancer-Associated Human Galectins

Galectins represent β-galactoside-binding proteins with numerous functions. Due to their role in tumor progression, human galectins-1, -3 and -7 (Gal-1, -3 and -7) are potential targets for cancer therapy. As plant derived glycans might act as galectin inhibitors, we prepared galactans by partial degradation of plant arabinogalactan-proteins. Besides commercially purchased galectins, we produced Gal-1 and -7 in a cell free system and tested binding capacities of the galectins to the galactans by biolayer-interferometry. Results for commercial and cell-free expressed galectins were comparable confirming functionality of the cell-free produced galectins. Our results revealed that galactans from Echinacea purpurea bind to Gal-1 and -7 with KD values of 1-2 µM and to Gal-3 slightly stronger with KD values between 0.36 and 0.70 µM depending on the sensor type. Galactans from the seagrass Zostera marina with higher branching of the galactan and higher content of uronic acids showed stronger binding to Gal-3 (0.08-0.28 µM) compared to galactan from Echinacea. The results contribute to knowledge on interactions between plant polysaccharides and galectins. Arabinogalactan-proteins have been identified as a new source for production of galactans with possible capability to act as galectin inhibitors

The effects of various respiratory physiotherapies after lung resection:a systematic review

PURPOSE: The purpose of this review was to investigate the effect of respiratory physiotherapy after lung resection on mortality, postoperative pulmonary complications (PPC), length of stay, lung volumes, and adverse events. MATERIAL AND METHODS: Randomized or quasi-randomized controlled trials were searched in CENTRAL, PubMed, EMBASE, Cinahl, PEDro, and hand searching of related studies. Various respiratory physiotherapy interventions were compared to standard care, sham treatment, or no treatment. Two reviewers assessed eligibility and quality of studies using Cochrane guidelines. Meta-analyses were undertaken on subgroups of intervention. RESULTS: Various types of positive pressure breathing, deep breathing exercises, and strength and aerobic exercises as a supplement to standard care did not show any significant effect over standard care in preventing mortality or PPC, reducing length of stay, or improving lung volumes. CONCLUSION: Prophylactic continuous positive airway pressure does not seem to affect rate of mortality and PPC, when compared with standard care embodying respiratory physiotherapy such as airway clearance techniques and assistance with early ambulation. However, further research is still needed to make a final conclusion. The effect of standard respiratory physiotherapy as a package is still unknown, and may or may not be effective in preventing PPC among patients undergoing lung resection

Die Hofstelle naturnah und attraktiv gestalten

Der Leitfaden bietet zahlreiche Anregungen und praktische Tipps für Landwirte zur naturnahen Gestaltung des Hofgeländes. Der Inhalt reicht von der Pflanzung von Gehölzen, der Begrünung von Fassaden und Dächern, Ideen für den Garten über die Gestaltung von Zäunen und Mauern oder der Nutzung von Wasser bis hin zur gezielten Förderung von Insekten, Vögeln und Fledermäusen

Cell Therapy for Prophylactic Tolerance in Immunoglobulin E-mediated Allergy

AbstractBackgroundTherapeutic strategies for the prophylaxis of IgE-mediated allergy remain an unmet medical need. Cell therapy is an emerging approach with high potential for preventing and treating immunological diseases.We aimed to develop a cell-based therapy inducing permanent allergen-specific immunological tolerance for preventing IgE-mediated allergy.MethodsWild-type mice were treated with allergen-expressing bone marrow cells under a short course of tolerogenic immunosuppression (mTOR inhibition and costimulation blockade). Bone marrow was retrieved from a novel transgenic mouse ubiquitously expressing the major grass pollen allergen Phl p 5 as a membrane-anchored protein (BALB/c-Tg[Phlp5-GFP], here mPhl p 5). After transplantation recipients were IgE-sensitized at multiple time points with Phl p 5 and control allergen.ResultsMice treated with mPhl p 5 bone marrow did not develop Phl p 5-specific IgE (or other isotypes) despite repeated administration of the allergen, while mounting and maintaining a strong humoral response towards the control allergen. Notably, Phl p 5-specific T cell responses and allergic airway inflammation were also completely prevented. Interestingly allergen-specific B cell tolerance was maintained independent of Treg functions indicating deletional tolerance as underlying mechanism.ConclusionThis proof-of-concept study demonstrates that allergen-specific immunological tolerance preventing occurrence of allergy can be established through a cell-based therapy employing allergen-expressing leukocytes

Green and fair economy – a holistic concept for a sustainable economy. Policy Brief #2013/02

Solution approaches based purely on economics do not lead to optimal success – at least, not in the medium to long term. Rather, a sustainable economy requires an equal consideration of the ecological and social dimensions. The green economy concept, or, better said, the green and fair economy concept, is in principle suitable for, if not avoiding an economic and financial crisis as experienced in the last five years, at least moderating its negative effects. The important thing here is to integrate the design of the concept as much as possible at the political, economic and individual level