Transient activation of dopaminergic neurons during development modulates visual responsiveness, locomotion and brain activity in a dopamine ontogeny model of schizophrenia.

It has been observed that certain developmental environmental risk factors for schizophrenia when modeled in rodents alter the trajectory of dopaminergic development, leading to persistent behavioural changes in adults. This has recently been articulated as the "dopamine ontogeny hypothesis of schizophrenia". To test one aspect of this hypothesis, namely that transient dopaminergic effects during development modulate attention-like behavior and arousal in adults, we turned to a small-brain model, Drosophila melanogaster. By applying genetic tools allowing transient activation or silencing of dopaminergic neurons in the fly brain, we investigated whether a critical window exists during development when altered dopamine (DA) activity levels could lead to impairments in arousal states in adult animals. We found that increased activity in dopaminergic neurons in later stages of development significantly increased visual responsiveness and locomotion, especially in adult males. This misallocation of visual salience and hyperactivity mimicked the effect of acute methamphetamine feeding to adult flies, suggesting up-regulated DA signaling could result from developmental manipulations. Finally, brain recordings revealed significantly reduced gamma-band activity in adult animals exposed to the transient developmental insult. Together, these data support the idea that transient alterations in DA signaling during development can permanently alter behavior in adults, and that a reductionist model such as Drosophila can be used to investigate potential mechanisms underlying complex cognitive disorders such as schizophrenia.

Effects of soil variability and weather conditions on pesticide leaching--a farm-level evaluation.

In line with European regulations, Dutch law imposes an environmental threshold of 0.1 microg L(-1) on pesticide concentrations in ground water. During registration, the risk of exceeding this threshold is assessed through simulations for one or a few standard scenarios that do not reflect spatial variability under field conditions. The introduction of precision agriculture, where soil variability is actively managed, can increase control over pesticide leaching. This study presents a step-wise evaluation of the effects of soil variability and weather conditions on pesticide leaching. The evaluation was conducted on a 100-ha arable farm and aimed at identifying opportunities for precision management. As a first step, a relative risk assessment identified pesticides presenting a relatively high risk to the environment. Second, the effect of weather conditions was analyzed through 20 years of simulations for three distinct soil profiles. Results were summarized in cumulative probability plots to provide a probabilistic characterization of historical weather data. The year matching 90% probability (1981) served as a reference to simulate pesticide leaching from 612 soil profiles. After interpolation, areas where concentrations exceeded the environmental threshold were identified. Out of a total of 19 pesticides, isoproturon [N-dimethyl-N'-(4-(1-methylethyl)phenyl)urea], metribuzin [4-amino-6-tert-butyl-3-(methylthio)-as-triazin-5(4H)-one], and bentazon [2,1,3-benzothiadiazin-4(3H)-one, 3-isopropyl-, 2,2-dioxide] showed the highest risk for leaching. Leaching was strongly affected by soil variability at the within-field, field, and farm levels. Opportunities for precision management were apparent, but depended on the scale level at which environmental thresholds were implemented. When legislation is formulated in this issue, the presented step-wise evaluation can serve as a basis for identification and precision management of high-risk pesticides.

Limb preservation in replantation surgery.

Five patients are presented in whom a traumatically amputated extremity or digit was perfused with oxygenated Fluosol DA-20%. Perfusion lasted between 16 and 46 hours. Microcirculatory oxygenation was monitored using pO2 measurements. Moreover, K¿lactate, glucose, and ATP levels were measured and electron microscopic sections of the vessels were investigated at the end of the experiment. All above-mentioned parameters suggest that the tissue was sufficiently provided with oxygen and viable after many hours of perfusion. Conclusive evidence of the viability of a perfused digit was given by its successful replantation after 17 hours of Fluosol perfusion (at approximately 15 degrees C).