Collagenous microstructure of the glenoid labrum and biceps anchor.

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Towards Safe and Sustainable Advanced (Nano)materials: A proposal for an early awareness and action system for advanced materials (Early4AdMa)

It is of utmost importance to develop an anticipatory risk governance approach and to proactively avoid the occurrence of potential unexpected risks of advanced (nano)materials. Addressing safety and sustainability issues early in the innovation chain can support innovation by preventing problems later on. Towards this goal, we propose a novel Early4AdMa system to systematically identify emerging issues of advanced nanomaterials. This system can be applied by regulators, risk assessors, as well as innovators

Modulation of Serotonin Transporter Function during Fetal Development Causes Dilated Heart Cardiomyopathy and Lifelong Behavioral Abnormalities

BACKGROUND: Women are at great risk for mood and anxiety disorders during their childbearing years and may become pregnant while taking antidepressant drugs. In the treatment of depression and anxiety disorders, selective serotonin reuptake inhibitors (SSRIs) are the most frequently prescribed drugs, while it is largely unknown whether this medication affects the development of the central nervous system of the fetus. The possible effects are the product of placental transfer efficiency, time of administration and dose of the respective SSRI. METHODOLOGY/PRINCIPAL FINDINGS: In order to attain this information we have setup a study in which these parameters were measured and the consequences in terms of physiology and behavior are mapped. The placental transfer of fluoxetine and fluvoxamine, two commonly used SSRIs, was similar between mouse and human, indicating that the fetal exposure of these SSRIs in mice is comparable with the human situation. Fluvoxamine displayed a relatively low placental transfer, while fluoxetine showed a relatively high placental transfer. Using clinical doses of fluoxetine the mortality of the offspring increased dramatically, whereas the mortality was unaffected after fluvoxamine exposure. The majority of the fluoxetine-exposed offspring died postnatally of severe heart failure caused by dilated cardiomyopathy. Molecular analysis of fluoxetine-exposed offspring showed long-term alterations in serotonin transporter levels in the raphe nucleus. Furthermore, prenatal fluoxetine exposure resulted in depressive- and anxiety-related behavior in adult mice. In contrast, fluvoxamine-exposed mice did not show alterations in behavior and serotonin transporter levels. Decreasing the dose of fluoxetine resulted in higher survival rates and less dramatic effects on the long-term behavior in the offspring. CONCLUSIONS: These results indicate that prenatal fluoxetine exposure affects fetal development, resulting in cardiomyopathy and a higher vulnerability to affective disorders in a dose-dependent manner

Excess of serotonin affects neocortical pyramidal neuron migration

The serotonin transporter (SERT) is a key molecule involved in the homeostasis of extracellular levels of serotonin and is regulated developmentally. Genetic deletion of SERT in rodents increases extracellular levels of serotonin and affects cellular processes involved in neocortical circuit assembly such as barrel cortex wiring and cortical interneuron migration. Importantly, pharmacological blockade of SERT during brain development leads to phenotypes relevant to psychiatry in rodents and to an increased risk for autism spectrum disorders in humans. Furthermore, developmental adversity interacts with genetically-driven variations of serotonin function in humans and nonhuman primates to increase the risk for a variety of stress-related phenotypes. In this study, we investigate whether an excess of serotonin affects the migration of neocortical pyramidal neurons during development. Using in utero electroporation combined with time-lapse imaging to specifically monitor pyramidal neurons during late mouse embryogenesis, we show that an excess of serotonin reversibly affects the radial migration of pyramidal neurons. We further identify that the serotonin receptor 5-HT6 is expressed in pyramidal neuron progenitors and that 5-HT6 receptor activation replicates the effects of serotonin stimulation. Finally, we show that the positioning of superficial layer pyramidal neurons is altered in vivo in SERT knockout mice. Taken together, these results indicate that a developmental excess of serotonin decreases the migration speed of cortical pyramidal neurons, affecting a fundamental step in the assembly of neural circuits. These findings support the hypothesis that developmental dysregulation of serotonin homeostasis has detrimental effects on neocortical circuit formation and contributes to increased vulnerability to psychiatric disorders

Slip in verankeringen hangerkabels voorkomen door betere bite

Op 22 januari 1999, kort voor ingebruikname van de Dintelhavenspoorbrug, bleek na een proefbelasting op de brug dat een aantal strengen van de hangerkabels door hun verankeringen waren geslipt. Dit was voor opdrachtgever Projectorganisatie Betuweroute aanleiding een onderzoekscommissie in te stellen, bestaande uit de auteurs van dit artikel. De hoofdoorzaak van het slippen van de strengen door hun verankeringen was de verkleving van de keggen aan de conusvormige gatwand van het ankerblok. De remedie tegen het slippen is gezocht in het alsnog genereren van de 'bite' van de keggen op de streng

Slip in verankeringen hangerkabels voorkomen door betere bite

Op 22 januari 1999, kort voor ingebruikname van de Dintelhavenspoorbrug, bleek na een proefbelasting op de brug dat een aantal strengen van de hangerkabels door hun verankeringen waren geslipt. Dit was voor opdrachtgever Projectorganisatie Betuweroute aanleiding een onderzoekscommissie in te stellen, bestaande uit de auteurs van dit artikel. De hoofdoorzaak van het slippen van de strengen door hun verankeringen was de verkleving van de keggen aan de conusvormige gatwand van het ankerblok. De remedie tegen het slippen is gezocht in het alsnog genereren van de 'bite' van de keggen op de streng