Human in vitro reporter model of neuronal development and early differentiation processes

<p>Abstract</p> <p>Background</p> <p>During developmental and adult neurogenesis, doublecortin is an early neuronal marker expressed when neural stem cells assume a neuronal cell fate. To understand mechanisms involved in early processes of neuronal fate decision, we investigated cell lines for their capacity to induce expression of doublecortin upon neuronal differentiation and develop <it>in vitro </it>reporter models using doublecortin promoter sequences.</p> <p>Results</p> <p>Among various cell lines investigated, the human teratocarcinoma cell line NTERA-2 was found to fulfill our criteria. Following induction of differentiation using retinoic acid treatment, we observed a 16-fold increase in doublecortin mRNA expression, as well as strong induction of doublecortin polypeptide expression. The acquisition of a neuronal precursor phenotype was also substantiated by the establishment of a multipolar neuronal morphology and expression of additional neuronal markers, such as Map2, βIII-tubulin and neuron-specific enolase. Moreover, stable transfection in NTERA-2 cells of reporter constructs encoding fluorescent or luminescent genes under the control of the doublecortin promoter allowed us to directly detect induction of neuronal differentiation in cell culture, such as following retinoic acid treatment or mouse Ngn2 transient overexpression.</p> <p>Conclusion</p> <p>Induction of doublecortin expression in differentiating NTERA-2 cells suggests that these cells accurately recapitulate some of the very early events of neuronal determination. Hence, the use of reporter genes under the control of the doublecortin promoter in NTERA-2 cells will help us to investigate factors involved early in the course of neuronal differentiation processes. Moreover the ease to detect the induction of a neuronal program in this model will permit to perform high throughput screening for compounds acting on the early neuronal differentiation mechanisms.</p

Natuerliche Geometrie und Dynamik

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Developing the college curriculum : a handbook for faculty &amp; administrators /

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Short-term annoyance from nocturnal aircraft noise exposure: results of the NORAH and STRAIN sleep studies

Purpose The German Aerospace Center (DLR) investigated in the NORAH sleep study the association between a distinct change in nocturnal aircraft noise exposure due to the introduction of a night curfew (11:00 pm-5:00 am) at Frankfurt Airport and short-term annoyance reactions of residents in the surrounding community. Exposure-response curves were calculated by using random effects logistic regression to evaluate the aircraft noise-related parameters (1) number of overflights and (2) energy equivalent noise level LASeq for the prediction of short-term annoyance. Data of the NORAH sleep study were compared with the STRAIN sleep study which was conducted by DLR near Cologne-Bonn Airport in 2001/2002 (N=64), representing a steady-state/low-rate change. Methods The NORAH sleep study was based on questionnaire surveys with 187 residents living in the vicinity of Frankfurt Airport. Noise-induced short–term annoyance and related non-acoustical variables were assessed. Nocturnal aircraft noise exposure was measured inside the residents` home. Results A statistically significant rise in the portion of annoyed residents with increasing number of overflights was found. Similarly, the portion of annoyed subjects increased with rising LASeq. Importance of the frequency of fly-overs for the prediction of annoyance reactions was emphasized. The annoyance probability was significantly higher in the NORAH than in the STRAIN sleep study. Conclusions Results confirm the importance of both acoustical parameters for the prediction of short-term annoyance due to nocturnal aircraft noise. Quantitative annoyance models that were derived at steady-state/low-rate change airports cannot be directly applied to airports that underwent a distinct change in operational and noise exposure patterns