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Newsletter - Fachbereich 03 – Gesellschaftswissenschaften : Ausgabe 2/2013 (2013)

Implantation of silicon dioxide-based nanocrystalline hydroxyapatite and pure phase beta-tricalciumphosphate bone substitute granules in caprine muscle tissue does not induce new bone formation (2013)

Shahram Ghanaati Samuel E. Udeabor Mike Barbeck Ines Willershausen Oliver Künzel Robert Alexander Sader C. James Kirkpatrick

Background: Osteoinductive bone substitutes are defined by their ability to induce new bone formation even at heterotopic implantation sites. The present study was designed to analyze the potential osteoinductivity of two different bone substitute materials in caprine muscle tissue. Materials and methods: One gram each of either a porous beta-tricalcium phosphate (β-TCP) or an hydroxyapatite/silicon dioxide (HA/SiO2)-based nanocrystalline bone substitute material was implanted in several muscle pouches of goats. The biomaterials were explanted at 29, 91 and 181 days after implantation. Conventional histology and special histochemical stains were performed to detect osteoblast precursor cells as well as mineralized and unmineralized bone matrix. Results: Both materials underwent cellular degradation in which tartrate-resistant acid phosphatase (TRAP)-positive osteoclast-like cells and TRAP-negative multinucleated giant cells were involved. The ß-TCP was completely resorbed within the observation period, whereas some granules of the HA-groups were still detectable after 180 days. Neither osteoblasts, osteoblast precursor cells nor extracellular bone matrix were found within the implantation bed of any of the analyzed biomaterials at any of the observed time points. Conclusions: This study showed that ß-TCP underwent a faster degradation than the HA-based material. The lack of osteoinductivity for both materials might be due to their granular shape, as osteoinductivity in goat muscle has been mainly attributed to cylindrical or disc-shaped bone substitute materials. This hypothesis however requires further investigation to systematically analyze various materials with comparable characteristics in the same experimental setting.

Comparing projections of future changes in runoff and water resources from hydrological and ecosystem models in ISI-MIP (2013)

Jemma C. S. Davie Peter D. Falloon Ron Kahana Rutger Dankers Richard Betts Felix Theodor Portmann Douglas B. Clark Akihiko Itoh Yoshimitsu Masaki Kazuya Nishina Balazs Fekete Zachary Tessler Xingcai Liu Qiuhong Tang Stefan Hagemann Tobias Stacke Ryan Pavlick Sibyll Schaphoff Simon N. Gosling Wietse Franssen Nigel Arnell

Projections of future changes in runoff can have important implications for water resources and flooding. In this study, runoff projections from ISI-MIP (Inter-sectoral Impact Model Intercomparison Project) simulations forced with HadGEM2-ES bias-corrected climate data under the Representative Concentration Pathway 8.5 have been analysed. Projections of change from the baseline period (1981–2010) to the future (2070–2099) from a number of different ecosystems and hydrological models were studied. The differences between projections from the two types of model were looked at globally and regionally. Typically, across different regions the ecosystem models tended to project larger increases and smaller decreases in runoff than the hydrological models. However, the differences varied both regionally and seasonally. Sensitivity experiments were also used to investigate the contributions of varying CO2 and allowing vegetation distribution to evolve on projected changes in runoff. In two out of four models which had data available from CO2 sensitivity experiments, allowing CO2 to vary was found to increase runoff more than keeping CO2 constant, while in two models runoff decreased. This suggests more uncertainty in runoff responses to elevated CO2 than previously considered. As CO2 effects on evapotranspiration via stomatal conductance and leaf-area index are more commonly included in ecosystems models than in hydrological models, this may partially explain some of the difference between model types. Keeping the vegetation distribution static in JULES runs had much less effect on runoff projections than varying CO2, but this may be more pronounced if looked at over a longer timescale as vegetation changes may take longer to reach a new state.

Range expansion of Ambrosia artemisiifolia in Europe is promoted by climate change (2013)

Sarah Cunze Marion Carmen Leiblein Oliver Tackenberg

Ambrosia artemisiifolia L., native to North America, is a problematic invasive species, because of its highly allergenic pollen. The species is expected to expand its range due to climate change. By means of ecological niche modelling (ENM), we predict habitat suitability for A. artemisiifolia in Europe under current and future climatic conditions. Overall, we compared the performance and results of 16 algorithms commonly applied in ENM. As occurrence records of invasive species may be dominated by sampling bias, we also used data from the native range. To assess the quality of the modelling approaches we assembled a new map of current occurrences of A. artemisiifolia in Europe. Our results show that ENM yields a good estimation of the potential range of A. artemisiifolia in Europe only when using the North American data. A strong sampling bias in the European Global Biodiversity Information Facility (GBIF) data for A. artemisiifolia causes unrealistic results. Using the North American data reflects the realized European distribution very well. All models predict an enlargement and a northwards shift of potential range in Central and Northern Europe during the next decades. Climate warming will lead to an increase and northwards shift of A. artemisiifolia in Europe.

Human CLPP reverts the longevity phenotype of a fungal ClpP deletion strain (2013)

Fabian Fischer Andrea Weil Andrea Hamann Heinz D. Osiewacz

Mitochondrial maintenance crucially depends on the quality control of proteins by various chaperones, proteases and repair enzymes. While most of the involved components have been studied in some detail, little is known on the biological role of the CLPXP protease complex located in the mitochondrial matrix. Here we show that deletion of PaClpP, encoding the CLP protease proteolytic subunit CLPP, leads to an unexpected healthy phenotype and increased lifespan of the fungal ageing model organism Podospora anserina. This phenotype can be reverted by expression of human ClpP in the fungal deletion background, demonstrating functional conservation of human and fungal CLPP. Our results show that the biological role of eukaryotic CLP proteases can be studied in an experimentally accessible model organism.

Dynamic and Volumetric Variables Reliably Predict Fluid Responsiveness in a Porcine Model with Pleural Effusion (2013)

Ole Broch Matthias Gruenewald Jochen Renner Patrick Meybohm Jan Schöttler Katharina Heß Markus Steinfath Berthold Bein

Background: The ability of stroke volume variation (SVV), pulse pressure variation (PPV) and global end-diastolic volume (GEDV) for prediction of fluid responsiveness in presence of pleural effusion is unknown. The aim of the present study was to challenge the ability of SVV, PPV and GEDV to predict fluid responsiveness in a porcine model with pleural effusions. Methods: Pigs were studied at baseline and after fluid loading with 8 ml kg−1 6% hydroxyethyl starch. After withdrawal of 8 ml kg−1 blood and induction of pleural effusion up to 50 ml kg−1 on either side, measurements at baseline and after fluid loading were repeated. Cardiac output, stroke volume, central venous pressure (CVP) and pulmonary occlusion pressure (PAOP) were obtained by pulmonary thermodilution, whereas GEDV was determined by transpulmonary thermodilution. SVV and PPV were monitored continuously by pulse contour analysis. Results: Pleural effusion was associated with significant changes in lung compliance, peak airway pressure and stroke volume in both responders and non-responders. At baseline, SVV, PPV and GEDV reliably predicted fluid responsiveness (area under the curve 0.85 (p<0.001), 0.88 (p<0.001), 0.77 (p = 0.007). After induction of pleural effusion the ability of SVV, PPV and GEDV to predict fluid responsiveness was well preserved and also PAOP was predictive. Threshold values for SVV and PPV increased in presence of pleural effusion. Conclusions: In this porcine model, bilateral pleural effusion did not affect the ability of SVV, PPV and GEDV to predict fluid responsiveness.

Newsletter 1/2013 / Institut für Sozialforschung an der Johann Wolfgang Goethe-Universität (2013)

How to target apoptosis signaling pathways for the treatment of pediatric cancers (2013)

Simone Fulda

Apoptosis represents one of the most important forms of cell death in higher organisms and is typically dysregulated in human cancers, including pediatric tumors. This implies that ineffective engagement of cell death programs can contribute to tumor formation as well as tumor progression. In addition, the majority of cytotoxic therapeutic principles rely on the activation of cell death signaling pathways in cancer cells. Blockade of signaling networks that lead to cell death can therefore confer treatment resistance. A variety of genetic and epigenetic events as well as dysfunctional regulation of signaling networks have been identified as underlying causes of cell death resistance in childhood malignancies. Apoptosis pathways can be therapeutically exploited by enhancing proapoptotic signals or by neutralizing antiapoptotic programs. The challenge in the coming years will be to successfully transfer this knowledge into the development of innovative treatment approaches for children with cancer.

Regulation of cell death in cancer - possible implications for immunotherapy (2013)

Simone Fulda

Since most anticancer therapies including immunotherapy trigger programmed cell death in cancer cells, defective cell death programs can lead to treatment resistance and tumor immune escape. Therefore, evasion of programmed cell death may provide one possible explanation as to why cancer immunotherapy has so far only shown modest clinical benefits for children with cancer. A better understanding of the molecular mechanisms that regulate sensitivity and resistance to programmed cell death is expected to open new perspectives for the development of novel experimental treatment strategies to enhance the efficacy of cancer immunotherapy in the future.

Advances in lens implant technology (2013)

Daniel Kook Anselm Kampik Alois K. Dexl Nicole Zimmermann Adrian Glasser Martin Baumeister Thomas Kohnen

Cataract surgery is one of the oldest and the most frequent outpatient clinic operations in medicine performed worldwide. The clouded human crystalline lens is replaced by an artificial intraocular lens implanted into the capsular bag. During the last six decades, cataract surgery has undergone rapid development from a traumatic, manual surgical procedure with implantation of a simple lens to a minimally invasive intervention increasingly assisted by high technology and a broad variety of implants customized for each patient’s individual requirements. This review discusses the major advances in this field and focuses on the main challenge remaining – the treatment of presbyopia. The demand for correction of presbyopia is increasing, reflecting the global growth of the ageing population. Pearls and pitfalls of currently applied methods to correct presbyopia and different approaches under investigation, both in lens implant technology and in surgical technology, are discussed.

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