Strategy selection during exploratory behavior: sex differences

This study was designed to assess sex-related differences in the selection of an appropriate strategy when facing novelty. A simple visuo-spatial task was used to investigate exploratory behavior as a specific response to novelty. The exploration task was followed by a visual discrimination task, and the responses were analyzed using signal detection theory. During exploration women selected a local searching strategy in which the metric distance between what is already known and what is unknown was reduced, whereas men adopted a global strategy based on an approximately uniform distribution of choices. Women's exploratory behavior gives rise to a notion of a secure base warranting a sense of safety while men's behavior does not appear to be influenced by risk. This sex-related difference was interpreted as a difference in beliefs concerning the likelihood of uncertain events influencing risk evaluation. Keywords: exploration, spontaneous strategies, sex differences, decision-making.

Scaling behavior and equilibrium lengths of knotted polymers

We use numerical simulations to investigate how the chain length and topology of freely fluctuating knotted polymer rings affect their various spatial characteristics such as the radius of the smallest sphere enclosing momentary configurations of simulated polymer chains. We describe how the average value of a characteristic changes with the chain size and how this change depends on the topology of the modeled polymers. Although the scaling profiles of a spatial characteristic for distinct knot types do not intersect (at least, in the range of our data), the profiles for nontrivial knots intersect the corresponding profile obtained for phantom polymers, i.e., those that are free to explore all available topological states. For each knot type, this point of intersection defines its equilibrium length with respect to the spatial characteristic. At this chain length, a polymer forming a given knot type will not tend to increase or decrease. on average, the value of the spatial characteristic when the polymer is released from its topological constraint. We show interrelations between equilibrium lengths defined with respect to spatial characteristics of different character and observe that they are related to the lengths of ideal geometric configurations of the corresponding knot types.

Gut-derived signaling molecules and vagal afferents in the control of glucose and energy homeostasis.

PURPOSE OF REVIEW: The control of glucose and energy homeostasis, including feeding behaviour, is tightly regulated by gut-derived peptidic and nonpeptidic endocrine mediators, autonomic nervous signals, as well as nutrients such as glucose. We will review recent findings on the role of the gastrointestinal tract innervation and of portal vein glucose sensors; we will review selected data on the action of gastrointestinally released hormones. RECENT FINDINGS: The involvement of mechanosensory vagal afferents in postprandial meal termination has been clarified using mouse models with selective impairments of genes required for development of mechanosensory fibres. These activate central glucogen-like peptide-1/glucogen-like peptide-2 containing ascending pathways linking the visceroceptive brainstem neurons to hypothalamic nuclei. Mucosal terminals comprise the chemosensory vagal afferents responsive to postprandially released gastrointestinal hormones. The mechanism by which the hepatoportal glucose sensor stimulates glucose utilization by muscles was demonstrated, using genetically modified mice, to be insulin-independent but to require GLUT4 and AMP-kinase. This sensor is a key site of glucogen-like peptide-1 action and plays a critical role in triggering first phase insulin secretion. PeptideYY and ghrelin target intracerebral receptors as they are bidirectionally transported across the blood brain barrier. The anorectic functions of peripherally released peptideYY may however be mediated both via vagal afferents and intracerebral Y2 receptors in the brainstem and arcuate nucleus. SUMMARY: These recent findings demonstrate that the use of improved anatomical and physiological techniques and animal models with targeted gene modifications lead to an improved understanding of the complex role of gastrointestinal signals in the control of energy homeostasis.

Sexual protection behavior in HIV-positive gay men: testing a modified information-motivation-behavioral skills model.

This study on determinants of sexual protection behavior among HIV-positive gay men used the empirically tested information-motivation-behavioral skills (IMB) model. HIV-specific variables were added to the model to determine factors decisive for condom use with steady and casual partners. Data were collected using an anonymous, standardized self-administered questionnaire. Study participants were recruited at HIV outpatient clinics associated with the Eurosupport Study Group and the Swiss HIV Cohort Study. To identify factors associated with condom use, backward elimination regression analyses were performed. Overall, 838 HIV-infected gay men from 14 European countries were included in this analysis. About 53% of them reported at least one sexual contact with a steady partner; 62.5% had sex with a casual partner during the last 6 months. Forty-three percent always used condoms with steady partners and 44% with casual partners. High self-efficacy and subjective norms in favor of condom-use were associated with increased condom use with casual and steady partners, whereas feeling depressed was associated with decreased condom use with casual partners. Condoms were used less often with HIV-positive partners. Self-efficacy as an important behavioral skill to perform protection behavior was influenced by lower perceived vulnerability, higher subjective norms, and more positive safer sex attitudes. The IMB-model constructs appeared to be valid; however, not all the model predictors could be determined as hypothesized. Besides the original IMB constructs, HIV-specific variables, including sexual partners' serostatus and mental health, explained condom use. Such factors should be considered in clinical interventions to promote "positive prevention."

Having Your Cake and Eating It, Too: Can Regulatory Agencies Be Both Independent and Accountable?

Independent regulatory agencies (IRAs) were created in various sectors and on different governmental levels to implement liberalization policies. This paper investigates the link between IRAs' independence, which is said to promote regulatory credibility and the use of technical expertise, and their accountability, which is related to the need for controlling and legitimizing independent regulators. The literature on the regulatory state anticipates a positive relation between the independence and accountability of IRAs, but systematic empirical evidence is still lacking. To tackle this question, this paper measures and compares the independence and the accountability of IRAs in three differentially liberalized sectors in Switzerland (telecommunications, electricity and railways). With the application of Social Network Analysis, this piece of research shows that IRAs can be de facto independent and accountable at the same time, but the two features do not necessarily co-evolve in the same direction.

Strategies of emotion regulation in adolescents and young adults with substance dependence or eating disorders

Some authors argue that both substance dependence and eating disorders should be considered as dependent behaviours. Similarities and differences between these disorders, however, remain unclear. This study compares processes of emotion regulation in adolescents and young adults (15 to 25 years old) with substance dependence (SD) or eating disorders (ED). One hundred and thirteen SD, 50 ED and 86 non-clinical subjects (NC), recruited in four French and Swiss locations, completed a self-report questionnaire of emotion regulation strategies. This questionnaire addresses the subjects' relationships, concerning past and present family, and refers to Main's (1990) concept of primary strategy (balanced activation and deactivation of attachment behaviours), and of secondary strategies (hyperactivation or excessive deactivation of the attachment system). Participants were also questioned in structured interviews, about life events and DSM-IV classification criteria. SD reported more adverse events than ED and NC. SD and ED reported using fewer primary strategies than NC, and SD had secondary strategies that were different from those of ED. Patients with eating disorders reported more hyperactivation, and SD reported more deactivation of the attachment system. It is hypothesized that while subjects with SD and ED have in common poorly regulated strategies, they differ in the way they process emotion or relationship-related information.

History of offending behavior in first episode psychosis patients: A marker of specific clinical needs and a call for early detection strategies among young offenders.

OBJECTIVES: Previous literature suggests that early psychosis (EP) patients with a history of offending behavior (HOB) have specific clinical needs. The aims of this study were to assess: (1) the prevalence of HOB in a representative sample of EP; (2) the premorbid and baseline characteristics of patients with HOB, and (3) the potential differences in short-term outcome of such patients when compared to patients without HOB. METHODS: The Early Psychosis Prevention and Intervention Centre (EPPIC) admitted 786 EP patients between 1998 and 2000. Data were collected from patients' files using a standardized questionnaire. Data of 647 patients could be analyzed. RESULTS: HOB patients (29% of the sample) were more likely to be male with lower level of premorbid functioning and education, have used illicit substances and have attempted suicide. They presented with a more complex clinical picture and had poorer 18-month outcome. Most importantly, they had a significantly longer duration of untreated psychosis. CONCLUSIONS: On the basis of the high prevalence and specific features of EP patients with HOB, our study confirms a need for additional research in this domain and for the development of specific treatment strategies. Most importantly, it suggests a need for the promotion of early detection strategies among the populations of young offenders, considering that some of them may be going through the early phases of a psychotic disorder and that reduction of treatment delay and provision of well adapted interventions may have a significant impact at numerous levels in such patients.

Attachment and temperament in early childhood; implications for later behavior problems.

In the context of a French validation study, the Child Behavior Checklist (CBCL) was administered to more than 3000 French speaking mothers of 5-year-old children. Scores were factor-analyzed. Principal components analysis revealed four dimensions: externalizing and internalizing behavior problems, immaturity and somatoform disorders. Another sample of 40 mothers participated in a longitudinal study, filling in the CBCL when their children were 5 years old. These children had been observed previously in the Strange Situation (SSP) at 21 months. Several dichotomous variables derived from the SSP (e.g. secure versus insecure, proximal versus distal interaction with the mother, avoidant behavior) have been used as predictors of the four dimensions extracted from the CBCL. Hierarchical regressions showed that proximal behaviors with the mother, which reflect temperamental characteristics independently of the quality of attachment, predicted internalizing problems, whereas avoidance of the mother, or insecure-avoidant attachment, predicted internalizing as well as externalizing problems at 5 years of age. These results show that attachment and temperament, as assessed by the SSP, may each have specific implications for later behavior problems.

Genetic and epigenetic analysis of SSAT gene dysregulation in suicidal behavior.

It has recently been proposed that the SSAT gene plays a role in the predisposition to suicidal behavior. SSAT expression was found to be down-regulated in the brain of suicide completers. In addition, a single nucleotide polymorphism (SNP) rs6526342 was associated both with variation in SSAT expression and with suicidal behavior. In this study, we aimed to characterize the relationship between SSAT dysregulation and suicide behavior. To this end, we measured SSAT expression levels in the ventral prefrontal cortex (VPFC) of suicide completers (n = 20) and controls (n = 20) and found them to be significantly down-regulated in suicide victims (P = 0.007). To identify the basis of the regulation of SSAT expression, we performed an association analysis of 309 SNPs with SSAT transcript levels in 53 lymphoblastoid cell lines from the CEPH collection. We then examined the methylation status of the SSAT promoter region in males and females suicide completers and control subjects whose SSAT brain expression had been measured. We found no evidence to support a role for SNPs in controlling the level of SSAT expression. SSAT promoter methylation levels were not different between suicide completers and controls and did not correlate with SSAT expression levels. In addition, we found no indication of a genetic association between suicidal behavior and SNPs located within the SSAT gene. Our study provides new results which show that dysregulation of SSAT expression does play a role in suicide behavior. However, our data do not support any association between rs6526342 and variation in SSAT expression or suicidal behavior.

Isolation of genetic mutation leading to abnormal phenotype in human through ultra-high-throughput sequencing (UHTS)

The introduction of Next Generation Sequencing (NGS) facilitated the task of localizing DNA variation and identifying the genetic cause of yet unsolved Mendelian disorders. Using Whole Exome Capture method and NGS, we identified the causative genetic aberration responsible for a number of monogenic disorders previously undetermined. Due to the novelty of the NGS method we benchmarked different algorithms to assess their merits and defects. This allowed us to establish a pipeline that we successfully used to pinpoint genes responsible for a form of West's syndrome, a Complex Intellectual Disability syndrome associated with patellar dislocation and celiac disease, and correcting some erroneous molecular diagnosis of Alport's syndrome in a Saudi Arabian family.

Insulinoma associated with a case of multiple endocrine neoplasia type I: Functional somatostatin receptors and abnormal glucose-induced insulin secretion.

A sporadic case of multiple endocrine neoplasia type I with coexisting insulinoma and hyperparathyroidism was investigated in vivo and in vitro. The insulinoma was localized by somatostatin receptor scintigraphy and these receptors were functionally active. Octreotide administration decreased the basal insulin and glucagon secretion by 90 and 46%, respectively. Immunocytochemistry of the insulinoma tissue was positive for insulin, chromogranin A and neuropeptide Y. The insulinoma cells were also isolated and cultured in vitro. Incubation experiments revealed that a low glucose concentration (1 mmol/l) was sufficient to increase cytosolic free calcium and to produce a maximal glucose-induced insulin release. Northern blot analysis of RNA obtained from the tumor showed a high abundance of the low Km glucose transporter GLUT1 but no transcript for the high Km glucose transporter GLUT2. The abnormal distribution of glucose transporters probably relates to the abnormal glucose sensing of insulinoma cells, and explains their sustained insulin secretion at low glucose concentrations. Whether these abnormalities share a pathogenetic link with the presence of functionally active somatostatin receptors remains to be elucidated.

Fluorescence imaging reveals the nuclear behavior of peroxisome proliferator-activated receptor/retinoid X receptor heterodimers in the absence and presence of ligand.

In a global approach combining fluorescence recovery after photobleaching (FRAP), fluorescence correlation spectroscopy (FCS), and fluorescence resonance energy transfer (FRET), we address the behavior in living cells of the peroxisome proliferator-activated receptors (PPARs), a family of nuclear receptors involved in lipid and glucose metabolism, inflammation control, and wound healing. We first demonstrate that unlike several other nuclear receptors, PPARs do not form speckles upon ligand activation. The subnuclear structures that may be observed under some experimental conditions result from overexpression of the protein and our immunolabeling experiments suggest that these structures are subjected to degradation by the proteasome. Interestingly and in contrast to a general assumption, PPARs readily heterodimerize with retinoid X receptor (RXR) in the absence of ligand in living cells. PPAR diffusion coefficients indicate that all the receptors are engaged in complexes of very high molecular masses and/or interact with relatively immobile nuclear components. PPARs are not immobilized by ligand binding. However, they exhibit a ligand-induced reduction of mobility, probably due to enhanced interactions with cofactors and/or chromatin. Our study draws attention to the limitations and pitfalls of fluorescent chimera imaging and demonstrates the usefulness of the combination of FCS, FRAP, and FRET to assess the behavior of nuclear receptors and their mode of action in living cells.

Insufficient coping behavior under chronic stress and vulnerability to psychiatric disorders

Epidemiological data indicate that 75% of subjects with major psychiatric disorders have their onset in the age range of 17-24 years. An estimated 35-50% of college and university students drop out prematurely due to insufficient coping skills under chronic stress, while 85% of students receiving a psychiatric diagnosis withdraw from college/university prior to the completion of their education. In this study we aimed at developing standardized means for identifying students with insufficient coping skills under chronic stress and at risk for mental health problems. A sample of 1,217 college students from 3 different sites in the U.S. and Switzerland completed 2 self-report questionnaires: the Coping Strategies Inventory "COPE" and the Zurich Health Questionnaire "ZHQ" which assesses "regular exercises", "consumption behavior", "impaired physical health", "psychosomatic disturbances", and "impaired mental health". The data were subjected to structure analyses by means of a Neural Network approach. We found 2 highly stable and reproducible COPE scales that explained the observed inter-individual variation in coping behavior sufficiently well and in a socio-culturally independent way. The scales reflected basic coping behavior in terms of "activity-passivity" and "defeatism-resilience", and in the sense of stable, socio-culturally independent personality traits. Correlation analyses carried out for external validation revealed a close relationship between high scores on the defeatism scale and impaired physical and mental health. This underlined the role of insufficient coping behavior as a risk factor for physical and mental health problems. The combined COPE and ZHQ instruments appear to constitute powerful screening tools for insufficient coping skills under chronic stress and for risks of mental health problems.