Toxic and Phenotypic Effects of AAV_Cre Used to Transduce Mesencephalic Dopaminergic Neurons

A popular approach to spatiotemporally target genes using the loxP/Cre recombination system is stereotaxic microinjection of adeno-associated virus (AAV) expressing Cre recombinase (AAV_Cre) in specific neuronal structures. Here, we report that AAV_Cre microinjection in the ventral tegmental area (VTA) of ErbB4 Cyt-1-floxed (ErbB4 Cyt-1^fl/fl) mice at titers commonly used in the literature (~10¹²–10¹³ GC/mL) can have neurotoxic effects on dopaminergic neurons and elicit behavioral abnormalities. However, these effects of AAV_Cre microinjection are independent of ErbB4 Cyt-1 recombination because they are also observed in microinjected wild-type (WT) controls. Mice microinjected with AAV_Cre (10¹²–10¹³ GC/mL) exhibit reductions of tyrosine hydroxylase (TH) and dopamine transporter (DAT) expression, loss of dopaminergic neurons, and they behaviorally become hyperactive, fail to habituate in the open field and exhibit sensorimotor gating deficits compared to controls microinjected with AAV_GFP. Importantly, these AAV_Cre non-specific effects are: (1) independent of serotype, (2) occur with vectors expressing either Cre or Cre-GFP fusion protein and (3) preventable by reducing viral titers by 1000-fold (10¹⁰ GC/mL), which retains sufficient recombination activity to target floxed genes. Our studies emphasize the importance of including AAV_Cre-injected WT controls in experiments because recombination-independent effects on gene expression, neurotoxicity and behaviors could be erroneously attributed to consequences of gene ablation.     

Tunable chirped fibre Bragg grating device controlled by variablemagnetic fields

A novel dynamic chirping fibre Bragg grating device based on a magnetic field applied to a magnetostrictive transducer capable of tuning its dispersion is presented. Chirping ranges up to 300 ps/nm have been demonstrated, which are suitable for several applications such as tunable transversal filtering and dynamic dispersion compensation     

Determining suitability of a fly ash for silica extraction and zeolite synthesis

Zeolitic material is obtained from fly ash both by direct conversion of the ash or from SiO₂ extracts obtained from fly ash. This study focuses on determining the suitability of a fly ash for SiO₂ extraction and for zeolite synthesis by direct conversion. The SiO₂ extraction experiments from different fly ashes show that the main parameters governing the SiO₂ extraction are: (a) a high bulk SiO₂ content (>52%, for obtaining an extraction yield of 100 g SiO₂ kg^?1) in the starting fly ash, (b) a high proportion (>55%) of the bulk SiO₂ present in the degradable glass matrix and the highly soluble opaline fraction, and (c) a high bulk SiO₂/Al₂O₃ ratio (>2.0) of the fly ash. The results from experiments of zeolite synthesis by direct conversion demonstrate that the most important criteria for the selection of a fly ash for this process are: (a) a high content of Al₂O₃ and SiO₂(>65%) (b) a high glass content (>63%) and (c) relatively low SiO₂/Al₂O₃ ratio (<2.0). Multivariate analysis confirms the importance of the above‐mentioned variables and shows some additional variables that have influence on ash behaviour under alkaline conditions. It quantifies the use of those variables for determining the suitability of ashes for SiO₂ extraction and zeolite synthesis and is able to distinguish between the two. Copyright © 2004 Society of Chemical Industry     

An epidemiological test of the hyperinsulinemia-hypertension hypothesis

The association between hyperinsulinemia and hypertension was tested in a population of 421 men and 228 women from the Baltimore Longitudinal Study of Aging. Subjects are white, middle-class, generally healthy, community-dwelling volunteers who ranged in age from 17-95 yr. Those with disease or medications known to influence any of the studied variables were excluded from the analysis. Twenty-five percent of the subjects were borderline or hypertensive [systolic blood pressure (BP) > or = 140 or diastolic BP > or = 90 mm Hg]. Standard oral glucose tolerance tests were performed; the logarithms of the fasting insulin level and insulin area were used in the analyses. In addition, body mass index and percent body fat (from age and skinfold thickness equations) and waist hip ratio were computed. In simple correlations, systolic BP and diastolic BP were statistically significantly related to insulin levels (only 1-4% of the variance was explained). Since age, body fat, fat distribution, insulin levels, and BP were highly intercorrelated, insulin and blood pressure correlations were examined after controlling for the confounding variables. Correlations of BP and insulin levels adjusted for age, body fat, and fat distribution were entirely nonsignificant. In this large noninterventive population study, the hyperinsulinemia-hypertension hypothesis is not confirmed.     

Separation of particulate solids in liquid magnetics and dielectrics

The orientation, spatial displacement and interaction of solid particles, in vacua and in liquid media, polarised in electrical and in magnetic fields, are computed. The separation effect in mixtures of particulate solids in the superimposed electromagnetic and gravitational fields is then analysed and the simple graphico-analytical method of positioning particles in superimposed fields is developed, with examples of such separations.