Retrieval-based skill learning: testing promotes the acquisition of scientific experimentation skills.

We investigated whether retrieval-based learning can facilitate the acquisition of cognitive skills, focusing on the control-of-variables strategy. This core scientific experimentation skill is regularly taught in science education classes because understanding it is essential for understanding experimental investigations in science. In the present study, participants initially read a text explaining the control-of-variables strategy. We compared the effects of subsequent retrieval practice and restudy of the text in performing a transfer test requiring the application of the control-of-variables strategy by judging the validity of a number of experimental designs. In addition, recall of the initially studied text was assessed as well. Repeated retrieval practice in combination with restudy opportunities resulted in better performance in both the transfer test and the recall test as compared to mere restudy or a single study opportunity. These findings demonstrate that retrieval practice is a useful tool for promoting deep conceptual learning.

[Trends in participation in nonformal education in the second half of life : Increasing educational participation in retirement]. / Trends in non-formaler Bildungsbeteiligung in der zweiten Lebenshälfte : Steigende Bildungsbeteiligung im Ruhestand.

BACKGROUND: Research on nonformal education often focuses on participation within employment. Participation of workers decreases with age; however, recent studies show an increase in participation in nonformal education of older workers. It remains, however, unclear if this trend spills over to retirement. OBJECTIVE: In the context of social change processes, trends in nonformal educational participation are analyzed. The study addresses employment and retirement as opportunity structures and investigates their impact on educational participation in the second half of life. METHODS: Predictors of educational participation are modeled in logistic regression, including interaction effects. Analyses are based on cross-sectional data of the German Ageing Survey and covers 20,129 respondents aged 40-85 years (T1: 1996 n = 4838; T2: 2002 n = 3084; T3: 2008 n = 6205; T4: 2014 n = 6002). RESULTS: Educational level, age, gender, employment status, region, social integration, and subjective health predict participation in nonformal education for people aged 40 to 85 years. Employment as an opportunity structure has a constant impact on participation, whereas retirees' participation increases over the course of time. CONCLUSIONS: The increase of retirees' participation in nonformal education is discussed in the context of social change processes and connected to theoretical und empirical research gaps with regard to educational participation in the second half of life.

Activity-guided screening of bioactive natural compounds implementing a new glucocorticoid-receptor-translocation assay and detection of new anti-inflammatory steroids from bacteria.

Using an in vitro cell-based assay in a flow-design, we have applied activity-guided screening to search for new bioactive compounds isolated from microorganisms. A first assay employs the stable expression of nuclear factor kappa B (NF-κB) while a second assay utilizes the glucocorticoid receptor (GR) coupled to green fluorescent protein. A specialized assay was implemented for both the translocation of NF-κB and to inhibit the translocation of cytokine-mediated NF-κB. In addition, we developed in a wide palette of cell lines used for a highly specialized GR-translocation assay to detect anti-inflammatory effects. This approach demonstrates the straight-forward combination of cell-based assays arranged with an automated fluorescence microscope. This allows for the direct sorting of extracts which are acting in a pharmaceutically interesting way. Initial results using this technique have led to the detection of new anti-inflammatory steroids from bacterial crude extracts.

Bendigoles D-F, bioactive sterols from the marine sponge-derived Actinomadura sp. SBMs009.

Marine derived actinomycetes have become an important source of bioactive natural products. Here we report the structure and bioactivity of the bendigoles D-F (1-3), 3-keto sterols isolated from the new marine sponge derived bacterium, Actinomadura sp. SBMs009. The isolation of these compounds was guided by a novel high-content screen for NF-κB and glucocorticoid receptor (GR) activity, and cytotoxicity assays. The structures of 1-3 were determined by detailed analysis of NMR, MS, and single crystal X-ray diffraction data. Interestingly, 1 displayed cytotoxicity against the L929 (mouse fibroblast) cell line with an IC(50) approximated to 30 µM and was the most active inhibitor of GR-translocation, while 3 was the most effective inhibitor of NF-κB nuclear translocation with an IC(50) of 71 µM.

Lack of correlation between NF-kappaB activation and induction of programmed cell death in PC12 pheochromocytoma cells treated with 6-hydroxydopamine or the cannabinoid receptor 1-agonist CP55,940.

NF-kappaB is a transcriptional regulator that plays a key role in immunity, inflammation and programmed cell death. We generated a PC12 cell line termed PC12kappaBluc that contains an integrated NF-kappaB-responsive reporter gene to directly measure NF-kappaB activity. The "classical" activators of NF-kappaB, phorbol 12-O-tetradecanoate-13-acetate and tumor necrosis factor alpha, strongly induced NF-kappaB activity in PC12kappaBluc cells. Activation of NF-kappaB could be attenuated by preincubating the cells with the cAMP analogue dbcAMP or via expression of the superrepressor IkappaBalphaS32A/S36A. PC12kappaBluc cells were subjected to several apoptotic paradigms, including treatment with 6-hydroxydopamine, H2O2, K2Cr2O7, MnCl2, C2-ceramide or the cannabinoid receptor-1 agonist CP55,940. A simultaneous measurement of the NF-kappaB activity revealed that only administration of 6-hydroxydopamine or CP55,940 increased NF-kappaB activity. Using pharmacological and genetic strategies to attenuate NF-kappaB transcriptional activity, we demonstrate that the elevation of NF-kappaB activity by 6-hydroxydopamine and CP55,940 is not an integral part of the apoptotic signaling cascade in PC12 cells.

Neuronal cell death induced by antidepressants: lack of correlation with Egr-1, NF-kappa B and extracellular signal-regulated protein kinase activation.

The tricyclic antidepressants (TCA) amitriptyline and desipramine and the serotonin reuptake inhibitor fluoxetine induce, at microM concentrations, cell death in HT22 immortalized hippocampal neurons and PC12 pheochromocytoma cells. Here, we show that these neurotoxic effects are accompanied by a selective activation of extracellular signal-regulated protein kinase (ERK), the biosynthesis of the transcription factor Egr-1 and an increase in the transcriptional activity of NF-kappa B. However, an impairment of both ERK activation and Egr-1 biosynthesis by the MAP kinase kinase-1 (MEK-1) inhibitor PD98059 did not block cell death. Moreover, stimulation of ERK phosphorylation and Egr-1 biosynthesis by sphingosine-1-phosphate did not induce cell death, indicating that stimulation of the ERK signaling pathway and Egr-1 biosynthesis are not required for neuronal cell death induced by antidepressants. Likewise, attenuation of antidepressant-induced NF-kappa B activity by elevation of the intracellular cAMP concentration or by retroviral driven expression of the non-degradable superrepressor I kappa B alpha S32A/S36A demonstrated that the elevation of NF-kappa B activity by amitriptyline, desipramine and fluoxetine is not an integral part of the apoptotic signaling cascade triggered by these compounds.

Epidermal growth factor and thrombin induced proliferation of immortalized human keratinocytes is coupled to the synthesis of Egr-1, a zinc finger transcriptional regulator.

The epidermal growth factor (EGF) receptor is highly expressed in HaCaT keratinocytes as shown by Western blotting. Stimulation of HaCaT cells with EGF, and also with the serine protease thrombin, induced DNA synthesis, measured by incorporation of 5-bromo-2'-deoxyuridine into the DNA of proliferating cells. Using antibodies directed against the active form of the EGF receptor, we show that in HaCaT cells EGF and thrombin triggered a rapid activation of the EGF receptor, followed by the phosphorylation and activation of the extracellular signal-regulated protein kinase (ERK). Moreover, EGF and thrombin induced a transient synthesis of the zinc finger transcriptional regulator Egr-1. Proliferation, activation of ERK, and biosynthesis of Egr-1 was completely inhibited in EGF or thrombin-treated HaCaT cells by the MAP kinase kinase inhibitor PD98059 and by AG1487, an EGF receptor-specific tyrosine kinase inhibitor. These data indicate that phosphorylation and activation of both the EGF receptor and ERK are essential for mitogenic signaling via EGF and thrombin. The synthesis of Egr-1 in HaCaT cells as a result of EGF or thrombin stimulation suggests that Egr-1 may be an important "late" part of the EGF and thrombin-initiated signaling cascades. We postulate that Egr-1 may function as a "third messenger" in keratinocytes connecting mitogenic stimulation with changes in gene transcription.