Effects of accumbens m-chlorophenylbiguanide microinjections on sleep and waking in intact and 6-hydroxydopamine-treated rats

Effects of the 5-HT3 receptor agonist, m-chlorophenylbiguanide (10.0-40.0 microg), on sleep and waking were studied in control, vehicle-treated and 6-hydroxydopamine-injected rats. Bilateral injections of m-chlorophenylbiguanide into the nucleus accumbens of the control and the vehicle-infused animals significantly increased waking and reduced slow wave sleep. Rapid eye movement sleep (REM sleep) remained unchanged. Pretreatment with the selective 5-HT3 receptor antagonist, MDL 72222 (1aH,3a,5a, H-tropan-3-yl-3,5-dichloro-benzoate) (0.5 mg/kg, s.c.), reversed the effects of m-chlorophenylbiguanide (10.0-20.0 microg) on sleep and waking in the control group. Administration of the 5-HT3 receptor agonist to the 6-hydroxydopamine-treated animals modified only slightly the time spent in wakefulness and slow wave sleep, while REM sleep was significantly and dose dependently reduced. Our findings further support the proposal that increase of wakefulness and reduction of slow wave sleep after activation of 5-HT3 receptors, is partly related to the release of endogenous dopamine.     

Combined Replenishment of miR‐34a and let‐7b by Targeted Nanoparticles Inhibits Tumor Growth in Neuroblastoma Preclinical Models

Neuroblastoma (NB) tumor substantially contributes to childhood cancer mortality. The design of novel drugs targeted to specific molecular alterations becomes mandatory, especially for high‐risk patients burdened by chemoresistant relapse. The dysregulated expression of MYCN, ALK, and LIN28B and the diminished levels of miR‐34a and let‐7b are oncogenic in NB. Due to the ability of miRNA‐mimics to recover the tumor suppression functions of miRNAs underexpressed into cancer cells, safe and efficient nanocarriers selectively targeted to NB cells and tested in clinically relevant mouse models are developed. The technology exploits the nucleic acids negative charges to build coated‐cationic liposomes, then functionalized with antibodies against GD₂ receptor. The replenishment of miR‐34a and let‐7b by NB‐targeted nanoparticles, individually and more powerfully in combination, significantly reduces cell division, proliferation, neoangiogenesis, tumor growth and burden, and induces apoptosis in orthotopic xenografts and improves mice survival in pseudometastatic models. These functional effects highlight a cooperative down‐modulation of MYCN and its down‐stream targets, ALK and LIN28B, exerted by miR‐34a and let‐7b that reactivate regulatory networks leading to a favorable therapeutic response. These findings demonstrate a promising therapeutic efficacy of miR‐34a and let‐7b combined replacement and support its clinical application as adjuvant therapy for high‐risk NB patients.     

Cascade Reactions: Sequential Homobimetallic Catalysis Leading to Benzofurans and β,γ‐Unsaturated Esters

The concatenation between a Pd(0)‐promoted deallylation catalytic cycle and a Pd(II)‐promoted heterocyclization catalytic cycle (an example of what we have named “sequential homobimetallic catalysis”) has been shown to occur starting from 1‐(2‐allyloxyphenyl)‐2‐yn‐1‐ols 1 to afford 2‐benzofuran‐2‐ylacetic esters 2 and β,γ‐unsaturated esters in high yields under carbonylative conditions. In view of the conceptual as well as the synthetic importance of the process, the mechanistic aspects and the synthetic scope of the reaction have been investigated in detail. All the experimental evidence is in agreement with the sequential homobimetallic mechanism, and the reaction has proven to be of general synthetic applicability.     

SiC Foams Decorated with SnO2 Nanostructures for Room Temperature Gas Sensing

Cell walls of the commercial silicon carbide (SiC)‐based foams were decorated by one‐dimensional tin dioxide (SnO₂) nanostructures. Thermal evaporation of SnO₂ powder with the assistance of a Au catalyst in inert atmosphere caused the formation of SnO₂ nanobelts on the pore surfaces. The room temperature (RT) ammonia (NH₃) and nitrogen dioxide (NO₂) gas sensing behaviors were investigated systematically in both dry and humid air atmosphere with/without UV activation. The results were compared to those for bare SnO₂ and SiC. It was shown that SiC/SnO₂ composite was efficient to detect low concentration of NH₃ (10–50 ppm) and NO₂ (1–5 ppm) under humid air and UV activation at RT.     

Induction of apoptosis in human neuroblastoma cells by abrogation of integrin-mediated cell adhesion

The survival, proliferation and differentiation of neuroblastoma (NB) cells are largely dependent on adhesion to extracellular matrix (ECM) proteins. Integrin occupancy seems to play a primary role. To elucidate the role of integrin heterodimers during neuronal cell death, we have analysed the changes in integrin expression in 2 human NB cell lines which represent different stages of neuronal maturation. Retinoic acid (RA) had different effects on the 2 NB cell lines: on LAN-5 cells it acted as a differentiation-promoting agent, while it had an anti-proliferative effect on GI-LI-N cells, driving them to apoptosis. Indeed, this occurrence was evidenced by the visualization of a "DNA ladder" on gel electrophoresis, by propidium iodide staining, and by DNA flow cytofluorimetric analysis. RA treatment rapidly and drastically decreased integrin expression and cell adhesion on GI-LI-N cells. These findings were also obtained by treating both NB cell lines with the apoptotic agent fenretinide. Furthermore, treatment of NB cells with anti-sense oligonucleotides to beta 1 integrin chain specifically induced chromatin condensation and nucleosomal DNA laddering. Moreover, blocking cell-matrix interactions by means of perturbing antibody against beta 1 subunit resulted in the induction of typical features of apoptotic cells. In conclusion, these findings indicate that abrogation of cell adhesion through down-modulation of integrin receptors plays a crucial role in the induction of neuroblastoma programmed cell death.     

Energie- und Ressourceneinsparung durch Innovative und CFD-basierte Auslegung von Flüssig/Flüssig-Schwerkraftabscheidern

Computational fluid dynamics (CFD) simulations in combination with droplet population balances lead to a practical standard for calculating the flow pattern – and thus the residence time distribution – in horizontal separators of any size based on available process data. The implementation of the droplet behavior also enables the calculation of a droplet-specific separator efficiency. The method development was carried out at identical plants at three different locations. The CFD simulations were successfully validated with experimental data from the participating industrial partners.     

SiOCN Functionalized Carbon Nanotube Gas Sensors for Elevated Temperature Applications

Silicon Oxycarbonitride (SiOCN) functionalization is proposed for stable, reproducible, reliable, and enhanced gas‐sensing properties in carbon nanotube (CNT) gas sensors. The process is very simple: liquid precursor completely coats the surfaces of the CNTs without requiring any surface modification and a thin layer of semiconductor ceramic SiOCN is created on the CNTs after heat treatment. This new kind of conductometric gas sensors can detect 10 ppm NH₃ and 2 ppm NO₂ at temperatures up to 350°C. The stability of the functionalized CNT sensor is verified up to 520°C, while the CNT sensor without the SiOCN coating lost conductance after 250°C due to the structural modification. SiOCN functionalization of CNT changes the recovery from irreversible to reversible and the recovery time decreases from 60 min at 100°C to 19 min at 350°C.