Orexin/hypocretin (Orx/Hcrt) transmission and drug-seeking behavior: is the paraventricular nucleus of the thalamus (PVT) part of the drug seeking circuitry?

The orexin/hypocretin (Orx/Hcrt) system has long been considered to regulate a wide range of physiological processes, including feeding, energy metabolism, and arousal. More recently, concordant observations have demonstrated an important role for these peptides in the reinforcing properties of most drugs of abuse. Orx/Hcrt neurons arise in the lateral hypothalamus (LH) and project to all brain structures implicated in the regulation of arousal, stress, and reward. Although Orx/Hcrt neurons have been shown to massively project to the paraventricular nucleus of the thalamus (PVT), only recent evidence suggested that the PVT may be a key relay of Orx/Hcrt-coded reward-related communication between the LH and both the ventral and dorsal striatum. While this thalamic region was not thought to be part of the "drug addiction circuitry," an increasing amount of evidence demonstrated that the PVT-particularly PVT Orx/Hcrt transmission-was implicated in the modulation of reward function in general and several aspects of drug-directed behaviors in particular. The present review discusses recent findings that suggest that maladaptive recruitment of PVT Orx/Hcrt signaling by drugs of abuse may promote persistent compulsive drug-seeking behavior following a period of protracted abstinence and as such may represent a relevant target for understanding the long-term vulnerability to drug relapse after withdrawal.

Real-time recording of circadian liver gene expression in freely moving mice reveals the phase-setting behavior of hepatocyte clocks.

The mammalian circadian timing system consists of a master pacemaker in the suprachiasmatic nucleus (SCN) in the hypothalamus, which is thought to set the phase of slave oscillators in virtually all body cells. However, due to the lack of appropriate in vivo recording technologies, it has been difficult to study how the SCN synchronizes oscillators in peripheral tissues. Here we describe the real-time recording of bioluminescence emitted by hepatocytes expressing circadian luciferase reporter genes in freely moving mice. The technology employs a device dubbed RT-Biolumicorder, which consists of a cylindrical cage with reflecting conical walls that channel photons toward a photomultiplier tube. The monitoring of circadian liver gene expression revealed that hepatocyte oscillators of SCN-lesioned mice synchronized more rapidly to feeding cycles than hepatocyte clocks of intact mice. Hence, the SCN uses signaling pathways that counteract those of feeding rhythms when their phase is in conflict with its own phase.

From Leadership to Citizenship Behavior in Public Organizations: When Values Matter

After decades of management reforms in the public sector, questions on the impact of leader-ship behavior in public organizations have been attracting increasing attention. This paper investigates the relationship between transformational leadership behavior and organizational citizenship behavior as one major extra-role outcome of transformational leadership. Refer-ring to a growing body of research that shows the importance of public service values and employee identification in public administration research, we include public service motiva-tion and organizational goal clarification as mediating variables in our analysis. Structural equation modeling is applied as the method of analysis for a sample of 569 public managers at the local level of Switzerland. The findings of our study support the assumed indirect relation-ship between leadership and employee behavior and emphasize the relevance of public ser-vice values when analyzing leadership behavior in public sector organizations.

Combined simulation and mutagenesis analyses reveal the involvement of key residues for peroxisome proliferator-activated receptor alpha helix 12 dynamic behavior.

The dynamic properties of helix 12 in the ligand binding domain of nuclear receptors are a major determinant of AF-2 domain activity. We investigated the molecular and structural basis of helix 12 mobility, as well as the involvement of individual residues with regard to peroxisome proliferator-activated receptor alpha (PPARalpha) constitutive and ligand-dependent transcriptional activity. Functional assays of the activity of PPARalpha helix 12 mutants were combined with free energy molecular dynamics simulations. The agreement between the results from these approaches allows us to make robust claims concerning the mechanisms that govern helix 12 functions. Our data support a model in which PPARalpha helix 12 transiently adopts a relatively stable active conformation even in the absence of a ligand. This conformation provides the interface for the recruitment of a coactivator and results in constitutive activity. The receptor agonists stabilize this conformation and increase PPARalpha transcription activation potential. Finally, we disclose important functions of residues in PPARalpha AF-2, which determine the positioning of helix 12 in the active conformation in the absence of a ligand. Substitution of these residues suppresses PPARalpha constitutive activity, without changing PPARalpha ligand-dependent activation potential.

Histological behavior of glutaraldehyde cross-linked bovine collagen injected into the human bladder for the treatment of vesicoureteral reflux

Endoscopic subureteral collagen injection has become an accepted means for the treatment of vesicoureteral reflux in children. The aim of this study was to evaluate the histological behavior of glutaraldehyde cross-linked bovine collagen implants. The specimens were harvested from 29 patients who underwent reimplant surgery 2 to 30 months (mean 9.5) after unsuccessful subureteral injection therapy. In addition to routine hematoxylin and eosin staining, a new staining method (solophenyl red 3BL) able to demonstrate selectively neoformation of types I and III human collagen, was applied. Invasion of host fibroblasts into the bovine implant and the formation of endogenous types I and III collagen were demonstrated in all 29 cases. Adverse histological reactions were rare and, if present, they were predominantly of an inflammatory nature.

Increased condom use without other major changes in sexual behavior among the general population in Switzerland.

The expression of DNA topoisomerase II alpha and beta genes was studied in murine normal tissues. Northern blot analysis using probes specific for the two genes showed that the patterns of expression were different among 22 tissues of adult mice. Expression levels of topoisomerase II alpha gene were high in proliferating tissues, such as bone marrow and spleen, and undetectable or low in 17 other tissues. In contrast, high or intermediate expression of topoisomerase II beta gene was found in a variety of tissues (15) of adult mice, including those with no proliferating cells. Topoisomerase II gene expression was also studied during murine development. In whole embryos both genes were expressed at higher levels in early than late stages of embryogenesis. Heart, brain and liver of embryos two days before delivery, and these same tissues plus lung and thymus of newborn (1-day-old) mice expressed appreciable levels of the two genes. Interestingly, a post-natal induction of the beta gene expression was observed in the brain but not in the liver; conversely, the expression of the alpha gene was increased 1 day after birth in the liver but not in the brain. However, gene expression of a proliferation-associated enzyme, thymidylate synthase, was similar in these tissues between embryos and newborns. Thus, the two genes were differentially regulated in the post-natal period, and a tissue-specific role may be suggested for the two isoenzymes in the development of differentiated tissues such as the brain and liver. Based on the differential patterns of expression of the two isoforms, this analysis indicates that topoisomerase II alpha may be a specific marker of cell proliferation, whereas topoisomerase II beta may be implicated in functions of DNA metabolism other than replication.

Do pornographic websites influence boys' sexual behavior?

Purpose: To compare the sexual behavior of adolescent males who do and do not watch pornographic websites. Methods: This study was presented as a school survey. Data were drawn from the 2002 Swiss Multicenter Adolescent Survey on Health (SMASH02) database, a survey including 7,548 adolescents age 16-20. The setting was post-mandatory schools in Switzerland. A total of 2,891 male students who connected to the internet in the last 30 days were enrolled and distributed into two groups: boys who deliberately watched pornographic websites in the last 30 days (n ¼ 942; 33%) and boys who did not (n ¼ 1,949; 67%). Socio-demographic characteristics; frequency of connection to the internet; sexual behavior parameters (having a girlfriend and if yes, for more or less than 6 months; having had sexual intercourse; age at first sexual intercourse; use of a condom at last sexual intercourse; number of sexual partners; having made a partner pregnant). Results: A logistic regression was performed using STATA 9.2. The only significant socio-demographic variable was having a low socioeconomic status (adjusted odds ratio [AOR] 1.66); no difference was found for age and academic track between the two groups. Boys who watch pornographic websites were also significantly more likely to connect frequently to the internet (one day a week: AOR 1.75; several days a week: AOR 2.36; every day: AOR 3.11), to have had sexual intercourse (AOR 2.06), and to have had their first sexual intercourse before age 15 (AOR 1.48). The stability of the relationship with their girlfriend did not appear to have any influence on the search for pornography on the internet. Conclusions: About one third of boys in our sample report having accessed pornographic websites in the last 30 days, a proportion similar to other studies. Watching such websites increases with the frequency of connection to the internet and seems to be correlated with an earlier sexual activity debut among adolescent males. However, having had first sexual intercourse before age 15 is the only sexual risk behavior that seems to be increased when watching pornographic websites among boys. Further studies should address the causality of this correlation and the factors influencing the search for pornography on the web among boys, in order to explore some new ways of prevention about sexual risk behaviors. Sources of Support: The SMASH02 survey was carried out with the financial support of the Swiss Federal Office of Public Health and the participating cantons.