Effects of corticotropin-releasing factor on brain serotonergic activity

The serotonergic dorsal raphe nucleus is innervated by corticotropin-releasing factor (CRF) and expresses CRF receptors, suggesting that endogenous CRF impacts on this system. The present study characterized interactions between CRF and the dorsal raphe serotonin (5-HT) system. The effects of intracerebroventricularly (i.c.v.) administered CRF on microdialysate concentrations of 5-HT in the lateral striatum of freely moving rats were determined. CRF had biphasic effects, with 0.1 and 0.3 microgram decreasing, and 3.0 micrograms increasing 5-HT dialysate concentrations. i.c.v. administration of CRF inhibited neuronal activity of the majority of dorsal raphe neurons at both low (0.3 microgram) and high (3 micrograms) doses. Likewise, intraraphe administration of CRF (0.3 and 1.0 ng) had predominantly inhibitory effects on discharge rate. Together, these results suggest that CRF is positioned to regulate the function of the dorsal raphe serotonergic system via actions within the cell body region. This regulation may play a role in stress-related psychiatric disorders in which 5-HT has been implicated.     

Localization of putative tumor suppressor loci by genome-wide allelotyping in human pancreatic endocrine tumors

Only two tumor suppressor gene loci, one on 3p25 and the MEN1 gene on 11q13, have thus far been implicated in the pathogenesis of sporadic human pancreatic endocrine tumors (PETs). A genome-wide allelotyping study of 28 human PETs was undertaken to identify other potential tumor suppressor gene loci. In addition to those on chromosomes 3p and 11q, frequent allelic deletions were identified on 3q (32%), 11p (36%), 16p (36%), and 22q (29%). Finer deletion mapping studies localized the smallest regions of common deletion to 3q27, 11p13, and 16p12.3-13.11. Potential candidate genes at these loci include WT1 (11p13), TSC2 (16p13), and NF2 (22q12), but no known tumor suppressor gene localizes to 3q27. The mean fractional allelic loss among these human PETs is 0.126, and no correlation was observed between allelic loss and clinical parameters, including age, sex, hormonal subtype, and disease stage. These findings highlight novel locations of tumor suppressor gene loci that contribute to the pathogenesis of human PETs, and several of these on 3p, 3q, and 22q are syntenic with loci on mouse chromosomes 9 and 16 that are implicated in a murine transgenic model of PETs.     

N-Methyl-D-aspartate attenuates opioid receptor-mediated G protein activation and this process involves protein kinase C

The effects of N-methyl-D-aspartate (NMDA) on opioid receptor-mediated G protein activation were explored in neuroblastoma X glioma hybrid (NG108-15) cells. Treatment of the cells with NMDA resulted in a remarkable attenuation of [35S]guanosine-5'-O-(3-thio)triphosphate binding stimulated by [D-Pen2,D-Pen5]-enkephalin (DPDPE), a delta-opioid receptor agonist. The effects of NMDA were dose and time dependent with an IC50 value of 5 nM and could be blocked by NMDA receptor antagonists. After NMDA treatment, the DPDPE dose-response curve shifted to the right (EC50 value increased approximately 7-fold, from 6 to 40 nM), and the maximal response induced by DPDPE was reduced by approximately 60%. The effects of NMDA were reversible, and the DPDPE response could recover within 60 min. The functional responses of delta-, mu-, and kappa-opioid receptors in primarily cultured neurons also were attenuated significantly by NMDA treatment. The inhibitory effects of NMDA on opioid receptor-mediated G protein activation could be blocked by coadministration of the protein kinase C (PKC) inhibitors or by elimination of the extracellular Ca2+. Correspondingly, NMDA treatment of NG108 cells significantly elevated cellular PKC activity and stimulated Gialpha2 phosphorylation. Transient transfection into NG108-15 cells of the wild-type Gialpha2 and a mutated Gialpha2 (Ser144Ala) resulted in a 2-fold increase in DPDPE-stimulated G protein activation. The DPDPE responses were greatly inhibited by NMDA treatment in the wild-type Gialpha2-transfected cells but much less affected in the mutant Gialpha2-transfected cells. In summary, NMDA attenuates opioid receptor/G protein coupling, and this process requires activation of PKC.     

The influence of stereoisomerism on the pharmacokinetics of Tc radiopharmaceuticals

The influence of stereoisomerism on the pharmacokinetics of Tc mono-oxo complexes is reviewed. Tc(V) monooxo complexes formed with N/S ligands have four donor groups from the ligands in an equatorial plane; the oxo ligand coordinates in an axial position. Stereoisomerism in Tc (V) mono-oxo complexes can be centered within the ligand (carbon atom in the chelate ring or ligating nitrogen of amine donors) or at the Tc. The metal center becomes chiral when an equatorial ligand has a head and a tail (i.e., the two ends of the ligand differ). All types of stereocenters can produce significantly different pharmacokinetic profiles for individual isomers. Thus, biological evaluation of separated stereoisomers is necessary to identify the optimal sterochemical configuration, particularly for radiopharmaceuticals targeted to receptor molecules with low specificity. Because of interspecies variation, there is ultimately no substitute for human testing. Although it is possible that the increase in non-specific binding of agents incorporating L-vs D-amino acids may more than offset any increased receptor binding, much more information is needed. Stereochemical factors can also lead to unpredictable differences in coordination geometry and thermodynamic preference of a single isomer; thus chemical characterization of stereoisomers continues to be an important component of radiopharmaceutical development.     

The relationship of individual and family factors to the psychological well-being of junior high school students living in urban poverty

This study examined the contribution of individual and family factors to psychological adjustment in a sample of junior high school students living in urban poverty. Identity development and perceived parental treatment were hypothesized to serve as mediating, or protective, factors between economic hardship and levels of self-esteem, depression, and loneliness. Consistent with the hypotheses, identity development did serve as a mediator between poverty and psychological adjustment. While perceived parental treatment was not related to economic hardship, it was clearly associated with well-being in this sample. Findings are discussed in terms of the differing contributions of family and individual development, as well as the importance of mediators in assessing the effects of poverty on young adolescents.     

Blowtooth: a provocative pervasive game for smuggling virtual drugs through real airport security

In this paper, we describe a pervasive game, Blowtooth, in which players use their mobile phones to hide virtual drugs on nearby airline passengers in real airport check-in queues. After passing through airport security, the player must find and recover their drugs from the innocent bystanders, without them ever realising they were involved in the game. The game explores the nature of pervasive game playing in environments that are not, generally, regarded as playful or “fun”. This paper describes the game’s design and implementation as well as an evaluation conducted with participants in real airports. It explores the players’ reactions to the game through questionnaire responses and in-game activity. The technologies used in Blowtooth are, intentionally, simple in order for the enjoyment of the game to be reliant more on the physical environment rather than the enabling technologies. We conclude that situating pervasive games in unexpected and challenging environments, such as international airports, may provide interesting and unique gaming experiences for players. In addition, we argue that pervasive games benefit most from using the specific features and nature of interesting real-world environments rather than focusing on the enabling technologies.     

Solvent extraction of metals from chloride solutions

A review is presented of a series of investigations into the extraction of copper, iron, zinc and cadmium into kerosene solutions of Lix or Kelex reagents from aqueous solutions containing chloride ions. The effects of chloride ions on the extraction of copper and iron were smaller than might have been expected to result from the formation of inextractable metal chlorocomplexes, and the extractants retained their selective properties. Extraction with Kelex 100 from chloride solution increased the separation between zinc and cadmium, in comparison with sulphate solutions.