µ-Opioid Receptors Expressed by Intrinsically Photosensitive Retinal Ganglion Cells Contribute to Morphine-Induced Behavioral Sensitization

Opioid drugs are the most effective tools for treating moderate to severe pain. Despite their analgesic efficacy, long-term opioid use can lead to drug tolerance, addiction, and sleep/wake disturbances. While the link between opioids and sleep/wake problems is well-documented, the mechanism underlying opioid-related sleep/wake problems remains largely unresolved. Importantly, intrinsically photosensitive retinal ganglion cells (ipRGCs), the cells that transmit environmental light/dark information to the brain’s sleep/circadian centers to regulate sleep/wake behavior, express μ-opioid receptors (MORs). In this study, we explored the potential contribution of ipRGCs to opioid-related sleep/circadian disruptions. Using implanted telemetry transmitters, we measured changes in horizontal locomotor activity and body temperature in mice over the course of a chronic morphine paradigm. Mice lacking MORs expressed by ipRGCs (McKO) exhibited reduced morphine-induced behavioral activation/sensitization compared with control littermates with normal patterns of MOR expression. Contrastingly, mice lacking MORs globally (MKO) did not acquire morphine-induced locomotor activation/sensitization. Control mice also showed morphine-induced hypothermia in both the light and dark phases, while McKO littermates only exhibited morphine-induced hypothermia in the dark. Interestingly, only control animals appeared to acquire tolerance to morphine’s hypothermic effect. Morphine, however, did not acutely decrease the body temperature of MKO mice. These findings support the idea that MORs expressed by ipRGCs could contribute to opioid-related sleep/wake problems and thermoregulatory changes.     

Fetal blood sampling--indication-related losses

The aim of this study, was to determine the fetal loss rate after fetal blood sampling (FBS) in relation to the indication. In total, 1981 FBS procedures (1878 pregnancies) were included, of which 117 were performed for the detection of congenital infection (group 1), 1437 for the detection of haemoglobinopathy (group 2), 233 for prenatal diagnosis with normal ultrasound findings (group 3), 121 for rapid karyotyping in cases with abnormal sonographic findings (group 4) and 73 for severe growth retardation (group 5). All the procedures were performed with a free-hand technique under continuous ultrasound guidance. Pregnancy losses occurring within two weeks of FBS were considered procedure-related losses. 343 pregnancies were terminated. Of the remaining 1535 continuing pregnancies, 73 (4.8 per cent) were lost, of which 39 (2.5 per cent) were lost within two weeks of the procedure. The procedure-related losses were 3 in 103 (2.9 per cent), 17 in 1090 (1.6 per cent), 2 in 191 (1 per cent), 11 in 84 (13.1 per cent) and 6 in 67 (8.9 per cent) in groups 1, 2, 3, 4 and 5, respectively. The differences in procedural loss between the five groups were highly significant, suggesting that the method entails a much higher risk when the fetus is structurally abnormal, or severely growth retarded. Patients should therefore be counselled before the procedure accordingly.     

Policies for the transition towards a hydrogen economy: the EU case

This paper reviews the current EU policy framework in view of its impact on hydrogen and fuel cell development. It screens EU energy policies, EU regulatory policies and EU spending policies. Key questions addressed are as follows: to what extent is the current policy framework conducive to hydrogen and fuel cell development? What barriers and inconsistencies can be identified? How can policies potentially promote hydrogen and fuel cells in Europe, taking into account the complex evolution of such a potentially disruptive technology? How should the EU policy framework be reformed in view of a strengthened and more coherent approach towards full deployment, taking into account recent technology-support activities?     

Effect of long‐term dietary administration of oregano and rosemary on the antioxidant status of rat serum,liver, kidney and heart after carbon tetrachloride‐induced oxidative stress

BACKGROUND: This study was performed on female Wistar rats allocated to eight groups of six animals each. Groups 1 and 2 were fed the basal diet, groups 3 and 4 were fed the basal diet supplemented with ground oregano at 20 g kg^?1 level, groups 5 and 6 were fed the basal diet supplemented with ground rosemary at 20 g kg^?1 level, while groups 7 and 8 were fed the basal diet supplemented with both oregano and rosemary, each at 20 g kg^?1 level. Following 6 weeks feeding, groups 2, 4, 6 and 8 were injected with CCl₄ at 1 mL kg^?1 body weight, and 6 h thereafter all animals were sacrificed. RESULTS: Administration of CCl₄ to the control rats enhanced (P < 0.05) aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP) activities, decreased cholesterol and triglycerides content in serum, increased (P < 0.05) lipid peroxidation and decreased (P < 0.05) the ABTS radical cation, the hydroxyl anion radical, the superoxide anion radical, and the hydrogen peroxide scavenging activities in all tested tissues, as compared to the control. Feeding oregano, rosemary or both before CCl₄ treatment resulted in decline (P < 0.05) of the increase in AST, ALT and ALP activities, increase (P < 0.05) of cholesterol and triglycerides in serum, decrease (P < 0.05) of lipid peroxidation, and increase (P < 0.05) of the ABTS radical cation, hydroxyl anion radical, superoxide anion radical and hydrogen peroxide scavenging activity. CONCLUSION: The results of this study suggest that long‐term dietary administration of oregano and rosemary has the potential to quench free radicals and alleviate CCl₄‐induced oxidative stress in rats. Copyright © 2009 Society of Chemical Industry     

Phase-aberration correction with a 3-D ultrasound scanner: feasibility study

We tested the feasibility of using adaptive imaging, namely phase-aberration correction, with two-dimensional (2-D) arrays and real-time, 3-D ultrasound. Because of the high spatial frequency content of aberrators, 2-D arrays, which generally have smaller pitch and thus higher spatial sampling frequency, and 3-D imaging show potential to improve the performance of adaptive imaging. Phase-correction algorithms improve image quality by compensating for tissue-induced errors in beamforming. Using the illustrative example of transcranial ultrasound, we have evaluated our ability to perform adaptive imaging with a real-time, 3-D scanner. We have used a polymer casting of a human temporal bone, root-mean-square (RMS) phase variation of 45.0 ns, full-width-half-maximum (FWHM) correlation length of 3.35 mm, and an electronic aberrator, 100 ns RMS, 3.76 mm correlation, with tissue phantoms as illustrative examples of near-field, phase-screen aberrators. Using the multilag, least-squares, cross-correlation method, we have shown the ability of 3-D adaptive imaging to increase anechoic cyst identification, image brightness, contrast-to-speckle ratio (CSR), and, in 3-D color Doppler experiments, the ability to visualize flow. For a physical aberrator skull casting we saw CSR increase by 13% from 1.01 to 1.14, while the number of detectable cysts increased from 4.3 to 7.7.     

Single-crystal organic charge-transfer interfaces probed using Schottky-gated heterostructures

Organic semiconductors based on small conjugated molecules generally behave as insulators when undoped, but the heterointerfaces of two such materials can show electrical conductivity as large as in a metal. Although charge transfer is commonly invoked to explain the phenomenon, the details of the process and the nature of the interfacial charge carriers remain largely unexplored. Here we use Schottky-gated heterostructures to probe the conducting layer at the interface between rubrene and PDIF-CN(2) single crystals. Gate-modulated conductivity measurements demonstrate that interfacial transport is due to electrons, whose mobility exhibits band-like behaviour from room temperature to ~150 K, and remains as high as ~1 cm(2) V(-1) s(-1) at 30 K for the best devices. The electron density decreases linearly with decreasing temperature, an observation that can be explained quantitatively on the basis of the heterostructure band diagram. These results elucidate the electronic structure of rubrene/PDIF-CN(2) interfaces and show the potential of Schottky-gated organic heterostructures for the investigation of transport in molecular semiconductors.     

Indole-3-Glycerol Phosphate Synthase From Mycobacterium tuberculosis: A Potential New Drug Target

Tuberculosis (TB), caused by the pathogen Mycobacterium tuberculosis, affects millions of people worldwide. Several TB drugs have lost efficacy due to emerging drug resistance and new anti-TB targets are needed. Recent research suggests that indole-3-glycerol phosphate synthase (IGPS) in M. tuberculosis (MtIGPS) could be such a target. IGPS is a (β/α)₈-barrel enzyme that catalyzes the conversion of 1-(o-carboxyphenylamino)-1-deoxyribulose 5’-phosphate (CdRP) into indole-glycerol-phosphate (IGP) in the bacterial tryptophan biosynthetic pathway. M. tuberculosis over expresses the tryptophan pathway genes during an immune response and inhibition of MtIGPS allows CD4 T-cells to more effectively fight against M. tuberculosis. Here we review the published data on MtIGPS expression, kinetics, mechanism, and inhibition. We also discuss MtIGPS crystal structures and compare them to other IGPS structures to reveal potential structure-function relationships of interest for the purposes of drug design and biocatalyst engineering.     

Factor structure of the Children’s Perception of Interparental Conflict Scale for studies of youths with externalizing behavior problems.

The assessment of children’s perception of marital conflict is an important area of research related to family relations, children’s cognitions about self, and the development of psychopathology. The leading instrument in this domain is the Children’s Perception of Interparental Conflict Scale (CPIC; J. H. Grych, M. Seid, & F. D. Fincham, 1992). It has 48 items organized into 9 conceptual designed subscales, with reports of 3-factor higher order structure to the 9 subscales. However, the 3-factor solution does not capture all 9 subscales well. Further, items have never been subjected to factor analysis to evaluate the best fitting factor structure at the item level. Doing so is particularly important when bringing the scale into new populations such as children with attention-deficit/hyperactivity disorder (ADHD) or disruptive behavior disorders. In the present study, 2 samples of children (total N = 1,190; ages 6–18 years) completed the CPIC. An exploratory factor analysis in Sample 1 (from a clinical study of ADHD and non-ADHD youths) yielded 4 interpretable factors. A confirmatory factor analysis in Sample 2 (a population sample of twins) confirmed the generalizability of the solution with an acceptable fit, although 1 item was dropped. The final solution used 38 of the 48 items. The 4-factor solution captured a Conflict Properties factor, two appraisal factors labeled Threat to Self and Self-Blame, and a Triangulation/Stability factor that included elements of appraisal and content. The authors concluded that the item-based 4-factor solution to the CPIC is preferable to the 9-factor or 3-factor formulation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Proof explanation for a nonmonotonic Semantic Web rules language

In this work, we present the design and implementation of a system for proof explanation in the Semantic Web, based on defeasible reasoning. Trust is a vital feature for Semantic Web. If users (humans and agents) are to use and integrate system answers, they must trust them. Thus, systems should be able to explain their actions, sources, and beliefs. Our system produces automatically proof explanations using a popular logic programming system (XSB), by interpreting the output from the proof’s trace and converting it into a meaningful representation. It also supports an XML representation for agent communication, which is a common scenario in the Semantic Web. In this paper, we present the design and implementation of the system, a RuleML language extension for the representation of a proof explanation, and we give some examples of the system. The system in essence implements a proof layer for nonmonotonic rules on the Semantic Web.     

SINGINT: Automatic numerical integration of singular integrands

We explore the combination of deterministic and Monte Carlo methods to facilitate efficient automatic numerical computation of multidimensional integrals with singular integrands. Two adaptive algorithms are presented that employ recursion and are runtime and memory optimized, respectively. SINGINT, a C implementation of the algorithms, is introduced and its utilization in the calculation of particle scattering amplitudes is exemplified.