During tissue invasion individual tumor cells exhibit two interconvertible migration modes, namely mesenchymal and amoeboid migration. The cellular microenvironment triggers the switch between both modes, thereby allowing adaptation to dynamic conditions. It is, however, unclear if this amoeboid-mesenchymal migration plasticity contributes to a more effective tumor invasion. We address this question with a mathematical model, where the amoeboid-mesenchymal migration plasticity is regulated in response to local extracellular matrix resistance. Our numerical analysis reveals that extracellular matrix structure and presence of a chemotactic gradient are key determinants of the model behavior. Only in complex microenvironments, if the extracellular matrix is highly heterogeneous and a chemotactic gradient directs migration, the amoeboid-mesenchymal migration plasticity allows a more widespread invasion compared to the non-switching amoeboid and mesenchymal modes. Importantly, these specific conditions are characteristic for in vivo tumor invasion. Thus, our study suggests that in vitro systems aiming at unraveling the underlying molecular mechanisms of tumor invasion should take into account the complexity of the microenvironment by considering the combined effects of structural heterogeneities and chemical gradients on cell migration.

The ability of humans to discriminate enantiomeric odour pairs is substance –specific. Current literature suggests that psychophysical discrimination of odour enantiomers mainly depends on the peripheral processing at the level of the olfactory sensory neurons (OSN). To study the influence of central processing in discrimination, we investigated differences in the electrophysiological responses to psychophysically indistinguishable (+)- and (−)- rose oxide enantiomers at peripheral and central-nervous levels in humans. We recorded the electro-olfactogram (EOG) from the olfactory epithelium and the EEG-derived olfactory event-related potentials (OERP). Results from a psychophysical three alternative forced choice test indicated indistinguishability of the two odour enantiomers. In a total of 19 young participants EOG could be recorded in 74 and OERP in 95% of subjects. Significantly different EOG amplitudes and latencies were recorded in response to the 2 stimuli. However, no such differences in amplitude or latency emerged for the OERP. In conclusion, although the pair of enantiomer could be discriminated at a peripheral level this did not lead to a central-nervous/cognitive differentiation of the two stimuli.

Research in younger adults dissociates cognitive from affective facets of social information processing, rather than promoting a monolithic view of social intelligence. An influential theory on adult development suggests differential effects of aging on cognitive and affective functions. However, this dissociation has not been directly tested in the social domain. Employing a newly developed naturalistic paradigm that disentangles facets of the social mind within an individual, we show multi-directionality of age-related differences. Specifically, components of the socio-cognitive route – Theory of Mind and metacognition – are impaired in older relative to younger adults. Nevertheless, these social capacities are still less affected by aging than factual reasoning and metacognition regarding non-social content. Importantly, the socio-affective route is well-functioning, with no decline in empathy and elevated compassion in the elderly. These findings contribute to an integrated theory of age-related change in social functioning and inform interventions tailored to specifically reinstate socio-cognitive skills in old age.

Drug repositioning identifies new indications for known drugs. Here we report repositioning of the malaria drug amodiaquine as a potential anti-cancer agent. While most repositioning efforts emerge through serendipity, we have devised a computational approach, which exploits interaction patterns shared between compounds. As a test case, we took the anti-viral drug brivudine (BVDU), which also has anti-cancer activity, and defined ten interaction patterns using our tool PLIP. These patterns characterise BVDU’s interaction with its target s. Using PLIP we performed an in silico screen of all structural data currently available and identified the FDA approved malaria drug amodiaquine as a promising repositioning candidate. We validated our prediction by showing that amodiaquine suppresses chemoresistance in a multiple myeloma cancer cell line by inhibiting the chaperone function of the cancer target Hsp27. This work proves that PLIP interaction patterns are viable tools for computational repositioning and can provide search query information from a given drug and its target to identify structurally unrelated candidates, including drugs approved by the FDA, with a known safety and pharmacology profile. This approach has the potential to reduce costs and risks in drug development by predicting novel indications for known drugs and drug candidates.

Die in der Reihe theorie.org erschienene Streitschrift Kritik des Familismus. Theorie und soziale Realität eines ideologischen Gemäldes von Gisela Notz diskutiert kritisch die Entwicklung des bundesdeutschen Familienbilds. Dabei entlarvt die Autorin dieses als ein ideologisch aufgeladenes und individuelle Freiheitsrechte einschränkendes Konstrukt, das äußerst persistent Geschlechter- und Arbeitsverhältnisse prägt.

Objectives Intra-articular injections of local anaesthetics (LA), glucocorticoids (GC), or hyaluronic acid (HA) are used to treat osteoarthritis (OA). Contrast agents (CA) are needed to prove successful intra-articular injection or aspiration, or to visualize articular structures dynamically during fluoroscopy. Tranexamic acid (TA) is used to control haemostasis and prevent excessive intra-articular bleeding. Despite their common usage, little is known about the cytotoxicity of common drugs injected into joints. Thus, the aim of our study was to investigate the effects of LA, GC, HA, CA, and TA on the viability of primary human chondrocytes and tenocytes in vitro. Methods Human chondrocytes and tenocytes were cultured in a medium with three different drug dilutions (1:2; 1:10; 1:100). The following drugs were used to investigate cytotoxicity: lidocaine hydrochloride 1%; bupivacaine 0.5%; triamcinolone acetonide; dexamethasone 21-palmitate; TA; iodine contrast media; HA; and distilled water. Normal saline served as a control. After an incubation period of 24 hours, cell numbers and morphology were assessed. Results Using LA or GC, especially triamcinolone acetonide, a dilution of 1:100 resulted in only a moderate reduction of viability, while a dilution of 1:10 showed significantly fewer cell counts. TA and CA reduced viability significantly at a dilution of 1:2. Higher dilutions did not affect viability. Notably, HA showed no effects of cytotoxicity in all drug dilutions. Conclusion The toxicity of common intra-articular injectable drugs, assessed by cell viability, is mainly dependent on the dilution of the drug being tested. LA are particularly toxic, whereas HA did not affect cell viability.

Facing poor long-term outcome and high relapse rates in the treatment of bulimia nervosa, we developed an Internet-based aftercare program for women with severe and chronic bulimia nervosa following inpatient treatment based on previous experiences with self-directed targeted prevention and early intervention programs delivered online. The aim of the present study was to examine adherence to the program in detail, to explore potential variables that predict adherence and to analyze whether adherence affects outcomes. We analyzed data from 126 women in the intervention group of a randomized controlled trial. 107 women (85%) logged on to the program platform at least once. These women opened on average 42.8% (SD=31.9%) of all assigned program pages. Adherence declined during the course of the intervention. Adherence was not associated with the number of outpatient treatment sessions received during the intervention period. Adherence was not related to overall illness severity or duration at baseline. However, excessive exercise at hospital discharge (which may be a sign of insufficient motivation to change eating disorder related behaviors) seems to play some small role in adherence. Adherence did not affect intervention outcomes. Based on our findings, we would like to advocate further research on online aftercare interventions for women with severe and chronic bulimia nervosa.

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