Thought conditioning : inducing and reducing thoughts about the aversive outcome in a fear-conditioning procedure

The human fear-conditioning paradigm is a widely used procedure to study anxiety. However, merely thinking about the aversive outcome is typically not measured in this procedure. This is surprising because thinking of an aversive event is of clinical relevance (e.g., in the form of intrusions) and theoretical interest. We present two preregistered studies that (a) included thinking of an aversive outcome as an additional dependent variable and (b) compared several interventions to reduce it. We found that mere thinking of an aversive outcome could be successfully conditioned. Among the participants who showed successful acquisition, extinction training was less successful in reducing it than counterconditioning. Presenting new additional outcomes also proved effective to reduce thoughts about the initial outcome when the new outcomes were positive stimuli. Including thinking of the aversive outcome as an additional dependent variable may serve to enhance the understanding of anxiety-related disorders and inform their treatment

Inducible reporter/driver lines for the Arabidopsis root with intrinsic reporting of activity state

International audienceCell-, tissue- or organ-specific inducible expression systems are powerful tools for functional analysis of changes to the pattern, level or timing of gene expression. However, plant researchers lack standardised reagents that promote reproducibility across the community. Here, we report the development and functional testing of a Gateway-based system for quantitatively, spatially and temporally controlling inducible gene expression in Arabidopsis that overcomes several drawbacks of the legacy systems. We used this modular driver/effector system with intrinsic reporting of spatio-temporal promoter activity to generate 18 well-characterised homozygous transformed lines showing the expected expression patterns specific for the major cell types of the Arabidopsis root; seed and plasmid vectors are available through the Arabidopsis stock centre. The system's tight regulation was validated by assessing the effects of diphtheria toxin A chain expression. We assessed the utility of Production of Anthocyanin Pigment 1 (PAP1) as an encoded effector mediating cell-autonomous marks. With this shared resource of characterised reference driver lines, which can be expanded with additional promoters and the use of other fluorescent proteins, we aim to contribute towards enhancing reproducibility of qualitative and quantitative analyses

Concomitant deficits in working memory and fear extinction are functionally dissociated from reduced anxiety in metabotropic glutamate receptor 7-deficient mice

Metabotropic glutamate receptor 7 (mGluR7), a receptor with a distinct brain distribution and a putative role in anxiety, emotional responding, and spatial working memory, could be an interesting therapeutic target for fear and anxiety disorders. mGluR7-deficient (mGluR7 / ) mice showed essentially normal performance in tests for neuromotor and exploratory activity and passive avoidance learning but prominent anxiolytic behavior in two anxiety tests. They showed a delayed learning curve during the acquisition of the hidden-platform water maze, and three interspersed probe trials indicated that mGluR7 / mice were slower to acquire spatial information. Working memory in the water maze task and the radial arm maze was impaired in mGluR7 / mice compared with mGluR7 / . mGluR7 / mice also displayed a higher resistance to extinction of fear-elicited response suppression in a conditioned emotional response protocol. In a non-fear-based water maze protocol, mGluR7 / mice displayed similar delayed extinction. These observed behavioral changes are probably not attributable to changes inAMPAorNMDAreceptor function because expression levels of AMPAand NMDA receptors were unaltered. Extinction of conditioned fear is an active and context-dependent form of inhibitory learning and an experimental model for therapeutic fear reduction. It appears to depend on glutamatergic and higher-level brain functions similar to those involved in spatial working memory but functionally dissociated from those that mediate constitutional responses in anxiety tests

Limitations of NOx removal by pulsed corona reactors

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Paul Eelen : reflections on life and work

This manuscript is part of a special issue to commemorate professor Paul Eelen, who passed away on August 21, 2016. Paul was a clinically oriented scientist, for whom learning principles (Pavlovian or operant) were more than salivary responses and lever presses. His expertise in learning psychology and his enthusiasm to translate this knowledge to clinical practice inspired many inside and outside academia. Several of his original writings were in the Dutch language. Instead of editing a special issue with contributions of colleagues and friends, we decided to translate a selection of his manuscripts to English to allow wide access to his original insights and opinions. Even though the manuscripts were written more than two decades ago, their content is surprisingly contemporary. This introductory article presents a reflection on Paul’s career and legacy and introduces the selected manuscripts that are part of this special issue

Fine structure, magnetic field and heating of sunspot penumbrae

We interpret penumbral filaments as due to convection in field-free, radially aligned gaps just below the visible surface of the penumbra, intruding into a nearly potential field above. This solves the classical discrepancy between the large heat flux and the low vertical velocities observed in the penumbra. The presence of the gaps causes strong small-scale fluctuations in inclination, azimuth angle and field strength, but without strong forces acting on the gas. The field is nearly horizontal in a region around the cusp-shaped top of the gap, thereby providing an environment for Evershed flows. We identify this region with the recently discovered dark penumbral cores. Its darkness has the same cause as the dark lanes in umbral light-bridges, reproduced in numerical simulations by Nordlund and Stein (2005). We predict that the large vertical and horizontal gradients of the magnetic field inclination and azimuth in the potential field model will produce the net circular polarization seen in observations. The model also explains the significant elevation of bright filaments above their surroundings. It predicts that dark areas in the penumbra are of two different kinds: dark filament cores containing the most inclined (horizontal) fields, and regions between bright filaments, containing the least inclined field lines.Comment: submitted to A&

The Potential Impact of Heparanase Activity and Endothelial Damage in COVID-19 Disease

SARS-CoV-2 was first detected in 2019 in Wuhan, China. It has been found to be the most pathogenic virus among coronaviruses and is associated with endothelial damage resulting in respiratory failure. Determine whether heparanase and heparan sulfate fragments, biomarkers of endothelial function, can assist in the risk stratification and clinical management of critically ill COVID-19 patients admitted to the intensive care unit. We investigated 53 critically ill patients with severe COVID-19 admitted between March and April 2020 to the University Hospital RWTH Aachen. Heparanase activity and serum levels of both heparanase and heparan sulfate were measured on day one (day of diagnosis) and day three in patients with COVID-19. The patients were classified into four groups according to the severity of ARDS. When compared to baseline data (day one), heparanase activity increased and the heparan sulfate serum levels decreased with increasing severity of ARDS. The heparanase activity significantly correlated with the lactate concentration on day one (r = 0.34, p = 0.024) and on day three (r = 0.43, p = 0.006). Heparanase activity and heparan sulfate levels correlate with COVID-19 disease severity and outcome. Both biomarkers might be helpful in predicting clinical course and outcomes in COVID-19 patients

MYCN-targeting miRNAs are predominantly downregulated during MYCN-driven neuroblastoma tumor formation

MYCN is a transcription factor that plays key roles in both normal development and cancer. In neuroblastoma, MYCN acts as a major oncogenic driver through pleiotropic effects controlled by multiple protein encoding genes as well as microRNAs (miRNAs). MYCN activity is tightly regulated at the level of transcription and protein stability through various mechanisms. Like most genes, MYCN is further controlled by miRNAs, but the full complement of all miRNAs implicated in this process has not been determined through an unbiased approach. To elucidate the role of miRNAs in regulation of MYCN, we thus explored the MYCN-miRNA interactome to establish miRNAs controlling MYCN expression levels. We combined results from an unbiased and genome-wide high-throughput miRNA target reporter screen with miRNA and mRNA expression data from patients and a murine neuroblastoma progression model. We identified 29 miRNAs targeting MYCN, of which 12 miRNAs are inversely correlated with MYCN expression or activity in neuroblastoma tumor tissue. The majority of MYCN-targeting miRNAs in neuroblastoma showed a decrease in expression during murine MYCN-driven neuroblastoma tumor development. Therefore, we provide evidence that MYCN-targeting miRNAs are preferentially downregulated in MYCN-driven neuroblastoma, suggesting that MYCN negatively controls the expression of these miRNAs, to safeguard its expression