Riluzole Attenuates L-DOPA-Induced Abnormal Involuntary Movements Through Decreasing CREB1 Activity

Chronic administration of L-DOPA, the first-line treatment of dystonic symptoms in childhood or in Parkinson's disease, often leads to the development of abnormal involuntary movements (AIMs), which represent an important clinical problem. Although it is known that Riluzole attenuates L-DOPA-induced AIMs, the molecular mechanisms underlying this effect are not understood. Therefore, we studied the behavior and performed RNA sequencing of the striatum in three groups of rats that all received a unilateral lesion with 6-hydroxydopamine in their medial forebrain bundle, followed by the administration of saline, L-DOPA, or L-DOPA combined with Riluzole. First, we provide evidence that Riluzole attenuates AIMs in this rat model. Subsequently, analysis of the transcriptomics data revealed that Riluzole is predicted to reduce the activity of CREB1, a transcription factor that regulates the expression of multiple proteins that interact in a molecular landscape involved in apoptosis. Although this mechanism underlying the beneficial effect of Riluzole on AIMs needs to be confirmed, it provides clues towards novel or existing compounds for the treatment of AIMs that modulate the activity of CREB1 and, hence, its downstream targets

Acoustic Estimation of Resonance Frequency and Sonodestruction of SonoVue Microbubbles

Acoustic properties of ultrasound (US) contrast agent microbubbles (MB) highly influence sonoporation efficiency and intracellular drug and gene delivery. In this study we propose an acoustic method to monitor passive and excited MBs in a real time. MB monitoring system consisted of two separate transducers. The first transducer delivered over an interval of 1 s US pulses (1 MHz, 1% duty cycle, 100 Hz repetition frequency) with stepwise increased peak negative pressure (PNP), while the second one continuously monitored acoustic response of SonoVue MBs. Pulse echo signals were processed according to the substitution method to calculate attenuation coefficient spectra and loss of amplitude. During US exposure at 50–100 kPa PNP we observed a temporal increase in loss of amplitude which coincided with the US delivery. Transient increase in loss of amplitude vanished at higher PNP values. At higher PNP values loss of amplitude decreased during the US exposure indicating MB sonodestruction. Analysis of transient attenuation spectra revealed that attenuation coefficient was maximal at 1.5 MHz frequency which is consistent with resonance frequency of SonoVue MB. The method allows evaluation of the of resonance frequency of MB, onset and kinetics of MB sonodestruction

Extraction of phenolic compounds from bilberry by-products left after pulsed electric field assisted juice production

By-products (press cake) resulting from PEF assisted juice production might still be exploited for recovery of valuable compounds. Therefore, the aim of this work was to investigate the effect of PEF pre-treatment of bilberry fruits on the recovery of phenolic compounds from the press cake left after the juice pressing. Mechanical pressing was used for juice extraction. The experiments were carried out at constant pressure (1.32 bar) using a lab-designed pressing chamber. PEF pre-treatments of constant electric field strength (3kV/cm) and varying specific energy (1-10 kJ/kg) or varying electric field strength (1-5 kV/kcm) and constant specific energy (10 kJ/kg) were applied to fresh bilberries prior to their pressing. Then the press cake left after the juice production was subjected to further extraction with acidified aqueous ethanol for 24 hours at ambient temperature. The total phenolic content of the extracts was determined using the Folin-Ciocalteu method [1]. The antioxidant activity of the extracts was tested using the FRAP assay [2]. Significantly higher amounts of total phenolics were extracted from the press cake of PEF-treated bilberries. The content of phenolic compounds extracted from the press cake of untreated (control) berries was 942 mg/100 g. The application of a PEF pre-treatment at 1, 3 and 5 kV/cm and constant specific energy yielded an increase in total phenolic content by 36%, 63% and 89%, respectively. When PEF pretreatment of constant electric field strength but varying energy input was applied to berries the total phenolic content in the press cake extracts was 58%, 56% and 63% higher for 1, 5 and 10 kJ/kg energy input, respectively. The PEF pre-treatment also resulted in significantly higher ferric reducing antioxidant power of the press cake extracts. In comparison to the control extract, PEF pre-treatments of berries at 1, 3 and 5 kV/cm increased the FRAP values of their press-cake extracts by 44%, 71% and 80%, respectively. Similarly, FRAP of press cake extracts obtained from PEF-treated bilberries at fixed electric field but varying energy input was from 40% (1 kJ/kg) to 71% (10 kJ/kg) higher. The results obtained from this study demonstrate that PEF pre-treatment of bilberries at higher intensity, both in terms of higher electric field strength or higher specific energy at fixed electric field strength resulted in better extractability of phenolic antioxidants from bilberry press cake left after the juice pressing. However, the increase in electric field strength had stronger impact on the extraction efficiency than the increase in delivered specific energy

The Development and Validation of the GMOAS, an Instrument Measuring Secondary School Students' Attitudes Towards Genetically Modified Organisms

FP7-SCIENCE-IN-SOCIETY-2007-1 Title: Digital support for Inquiry, Collaboration, and Reflection on Socio-Scientific DebatesGenetically modified organisms (GMOs) is a rapidly evolving area of scientific innovation and an issue receiving global attention. Attempts to devise usable instruments that assess people's attitudes towards this innovation have been rare and non-systematic. The aim of this paper is to present the development and validation of the genetically modified organisms attitudes scale (GMOAS), an instrument measuring secondary school students' attitudes towards GMOs. The responses of 1,111 secondary school students from Cyprus were used to validate the instrument. Principal component analysis with varimax rotation revealed a clear three-factor solution explaining 45.8% of the total variance. The factors underlying the attitudes' construct are: GMO implications on health, Interest in the topic of GMOs, and GMO implications on the environment. The 16-item, five-point Likert-type GMOAS showed satisfactory internal consistency and discriminant validity. When the instrument was used to analyse data from Cyprus, results revealed that Cypriot secondary school students have rather non-supportive attitudes towards the cultivation and use of GMOs. Male students were less negative in using GMOs for health and environmental purposes than females. Females, however, were found to be more interested in learning about GMOs. These findings comply with the rather country-specific nature of GMO attitudes