The Fight against Cancer by Microgravity: The Multicellular Spheroid as a Metastasis Model

Cancer is a disease exhibiting uncontrollable cell growth and spreading to other parts of the organism. It is a heavy, worldwide burden for mankind with high morbidity and mortality. Therefore, groundbreaking research and innovations are necessary. Research in space under microgravity (µg) conditions is a novel approach with the potential to fight cancer and develop future cancer therapies. Space travel is accompanied by adverse effects on our health, and there is a need to counteract these health problems. On the cellular level, studies have shown that real (r-) and simulated (s-) µg impact survival, apoptosis, proliferation, migration, and adhesion as well as the cytoskeleton, the extracellular matrix, focal adhesion, and growth factors in cancer cells. Moreover, the µg-environment induces in vitro 3D tumor models (multicellular spheroids and organoids) with a high potential for preclinical drug targeting, cancer drug development, and studying the processes of cancer progression and metastasis on a molecular level. This review focuses on the effects of r- and s-µg on different types of cells deriving from thyroid, breast, lung, skin, and prostate cancer, as well as tumors of the gastrointestinal tract. In addition, we summarize the current knowledge of the impact of µg on cancerous stem cells. The information demonstrates that µg has become an important new technology for increasing current knowledge of cancer biology.     

Influence of Methanol on Prion Reduction during High Temperature and High Pressure Oleochemical Processes

Prion‐reduction in standard biodiesel processes is caused by acidic and alkaline conditions. In the alternative RepCat biodiesel process, efficient prion‐reduction can be achieved by high‐temperature/pressure. However, a possible increase in thermostability of prions in the presence of methanol during these conditions has not previously been investigated, and is verified in this work. Samples are spiked with prions, treated with methanol, and incubated at 220 °C at 80 bar for 30 min. No traces of protease‐resistant prion protein (as proxy for prions) are detected in tallow or glycerine (as the final by‐product) after treatment. Serial dilutions of spiked prions show at least 6 log₁₀ prion reduction. More importantly, similar effects are detected using milder conditions of 200 °C at 70 bar for 15 min, representing the worst‐case conditions of the process. In conclusion, this study shows that methanol does not increase the thermostability of prions and the RepCat process can efficiently eliminate prions and is therefore safe for the usage of category 1 tallow. Practical Applications: The study further supports the applicability of RepCat process in reducing prion‐contamination in the presence of methanol. Furthermore, the conditions leads to a considerable reduction of prions in glycerine obtained as by‐product.     

Attentional sensitization of unconscious cognition: Task sets modulate subsequent masked semantic priming.

According to classical theories, automatic processes are autonomous and independent of higher level cognitive influence. In contrast, the authors propose that automatic processing depends on attentional sensitization of task-congruent processing pathways. In 3 experiments, the authors tested this hypothesis with a modified masked semantic priming paradigm during a lexical decision task by measuring event-related potentials (ERPs): Before masked prime presentation, participants attended an induction task either to semantic or perceptual stimulus features designed to activate a semantic or perceptual task set, respectively. Semantic priming effects on the N400 ERP component, an electrophysiological index of semantic processing, were obtained when a semantic task set was induced immediately before subliminal prime presentation, whereas a previously induced perceptual task set attenuated N400 priming. Across experiments, comparable results were obtained regardless of the difficulty level and the verbal or nonverbal nature of the induction tasks. In line with the proposed attentional sensitization model, unconscious semantic processing is enhanced by a semantic and attenuated by a perceptual task set. Hence, automatic processing of unconscious stimuli is susceptible to top-down control for optimizing goal-related information processing. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The Role of Oncostatin M and Its Receptor Complexes in Cardiomyocyte Protection,Regeneration, and Failure

Oncostatin M (OSM), a member of the interleukin-6 family, functions as a major mediator of cardiomyocyte remodeling under pathological conditions. Its involvement in a variety of human cardiac diseases such as aortic stenosis, myocardial infarction, myocarditis, cardiac sarcoidosis, and various cardiomyopathies make the OSM receptor (OSMR) signaling cascades a promising therapeutic target. However, the development of pharmacological treatment strategies is highly challenging for many reasons. In mouse models of heart disease, OSM elicits opposing effects via activation of the type II receptor complex (OSMR/gp130). Short-term activation of OSMR/gp130 protects the heart after acute injury, whereas chronic activation promotes the development of heart failure. Furthermore, OSM has the ability to integrate signals from unrelated receptors that enhance fetal remodeling (dedifferentiation) of adult cardiomyocytes. Because OSM strongly stimulates the production and secretion of extracellular proteins, it is likely to exert systemic effects, which in turn, could influence cardiac remodeling. Compared with the mouse, the complexity of OSM signaling is even greater in humans because this cytokine also activates the type I leukemia inhibitory factor receptor complex (LIFR/gp130). In this article, we provide an overview of OSM-induced cardiomyocyte remodeling and discuss the consequences of OSMR/gp130 and LIFR/gp130 activation under acute and chronic conditions.     

Genetically Encoded Libraries of Constrained Peptides

Many therapeutic peptides can still be improved with respect to target specificity, target affinity, resistance to peptidases/proteases, physical stability, and capacity to pass through membranes required for oral delivery. Several modifications can improve the peptides’ properties, in particular those that impose (a) conformational constraint(s). Screening of constrained peptides and the identification of hits is greatly facilitated by the generation of genetically encoded libraries. Recent breakthrough bacterial, phage, and yeast display screening systems of ribosomally synthesized post-translationally constrained peptides, particularly those of lanthipeptides, are earning special attention. Here we provide an overview of display systems for constrained, genetically encoded peptides and indicate prospects of constrained peptide-displaying phage and bacterial systems as such in vivo.     

Fluidized Bed Air Drying: Experimental Study and Model Development

The presented study describes the processes and mechanisms of batch fluidized bed drying. The influencing factors of hot air drying are theoretically and experimentally examined, in order to present the relations between temperature and humidity profiles and all other drying parameters. A physical model is presented to facilitate the calculation of the drying processes under defined conditions. Three succeeding drying stages are therefore modeled. Mass and energy balances including all components taking part in the process are formulated. The model clarities the drying process under the assumption of pure heat transfer mechanisms. It does not contain adaptive parameters and takes into account an inactive bypass fraction of the fluidization and drying medium. The evaluation of the model was successful for two fluidized bed plants with nominal widths of 100 mm and 400 mm. The experiments showed sufficient accuracy and transferability of the model to equipment of application‐oriented dimensions.     

The influence of various reaction parameters on the performance of (α‐diimine)nickel(II) catalysts in ethylene oligomerization reactions

Modified (α‐diimine)nickel(II) catalysts are suitable for ethylene oligomerization reactions. Due to the mechanism (“chain running”), the formation of double‐bond isomers and branched olefins can be observed. The obtained oligomer mixtures show a Schulz–Flory distribution. Increasing ethylene pressure favors the selectivity of α‐olefin formation. The same effect can be observed when Lewis bases like thiophene or furane are added to the oligomerization reaction mixture. These results can be related to an interaction of the additives with the catalytic active species during the oligomerization process. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 1356–1361, 2003     

Entwicklung und Erprobung eines Wäschersystems zur CO2‐Abreinigung aus Rauchgasen mithilfe alkalischer Reststoffe

An innovative, technical approach for the reduction of CO₂ emissions is presented that utilizes alkaline wastes to capture CO₂ from flue gases in stable mineral form. Comprehensive pilot‐scale experiments were conducted with the developed flue gas scrubbing system at a power plant site. By optimizing the process parameters gas flux, CO₂ partial pressure, circulation flux and suspension liquid‐to‐solid ratio, a CO₂ binding of 40 – 90 g kg^–1 waste could be reached and up to 25 % of the CO₂ could be captured. The new technique is economically advantageous especially when both alkaline waste and CO₂ are produced on site and when the carbonated products can be used as secondary resources.     

Investigation of the phase separation of PNIPAM using infrared spectroscopy together with multivariate data analysis

The use of vibrational spectroscopy to investigate complex structural changes in polymers yields chemically rich data, but interpretation can be challenging and subtle but meaningful spectral changes may be missed through visual inspection alone. Multivariate analysis is an efficient approach to gain an oversight of small but systematic spectral differences anywhere within the spectra, providing further insight into structural changes and associated transformation mechanisms. In this study, the novel analytical approach of infrared spectroscopy combined with principal component analysis and Gaussian peak fitting was used to investigate the structural changes in aqueous solutions of a polymer, using poly(N-isopropyl acrylamide) (PNIPAM) in the atactic form and with controlled tacticity as a model system. Subtle spectral changes associated with the dehydration and phase separation upon heating included peak shifts, an area ratio change of the amide I band to the amide II band and formation of a new peak in the amide I band were efficiently detected. Dehydration and phase separation of PNIPAM occurred in two temperature ranges, one for the atactic and one for isotactic rich part, both involving a complex re-organization of the hydrogen bonds and change of the hydration layer. The changes agreed with existing results from other techniques, and new insights were gained into the effect of controlled tacticity on phase transformation behaviour. The study demonstrates that infrared spectroscopy combined with the multivariate analytical method principal component analysis and Gaussian peak fitting is an efficient approach to probing structural change in polymers during heating. The simplicity of the presented approach could find excellent use in analysing and understanding the molecular environment of a range of stimuli-responsive polymers, for instance block or grafted types of polymers, as well as those with controlled tacticity.