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.     

Mental visualization before and after problem presentation: a comparison

Three experiments were carried out to study the effects on problem solving of visualization when subjects (secondary-school students and undergraduates) were instructed to generate mental images before the problem was presented and when they received such a hint after being given the problem. In each experiment an arithmetic, a geometric, and a practical problem were presented in three different conditions, a control condition, an "imagery-before" condition, and an "imagery-after" condition. Analysis showed that, in general, the "imagery-after" task helps subjects to overcome the misleading or fixating tendencies which interfere with problem solution; in contrast, the "imagery-before" task may enhance such tendencies.     

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.     

Bonded aerospace repairs under tensile loading: Wet chemical surface treatment and selected environmental conditions

Repair of composite structures and the impact of demanding environmental conditions is a crucial issue for the aircraft industry because of the increasing use of composites in modern aircraft. Consequently, the impact of environmental conditions common for aircraft applications on repair specimens in comparison to nonrepaired specimens is studied. All specimens are produced from a woven carbon fiber-reinforced epoxy-based prepreg. For the repair-specimens, an epoxy-based film adhesive is used for the soft patch repair approach. During the repair process, the surface of the precured prepreg is prepared by a mechanical method (sanding) and an additional chemical functionalization, respectively. Moisture absorption of the repair specimens is independent of the surface preparation method and higher for the repaired than for the nonrepaired specimens. The key influencing environmental conditions for the tensile strength and the failure mode of the repair specimens are elevated temperature testing as well as hot/wet conditioning and conditioning in deionized water. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 47506.     

Computational spectroscopy and reaction dynamics

Physico- and bio-chemical processes on the femto- to picosecond time scale are ideally suited to be investigated with all-atom simulations. They include, amongst others, vibrational relaxation, ligand migration in sterically demanding environments (proteins, ices), or vibrational spectra. By comparing with experimental data, the results can be used to obtain an understanding of the mechanisms underlying the observations. Furthermore, most of these processes are sensitive to the intermolecular interactions. Therefore, detailed refinement of such interaction potentials is possible.