Lateral prefrontal model-based signatures are reduced in healthy individuals with high trait impulsivity

High impulsivity is an important risk factor for addiction with evidence from endophenotype studies. In addiction, behavioral control is shifted toward the habitual end. Habitual control can be described by retrospective updating of reward expectations in ‘model-free’ temporal-difference algorithms. Goal- directed control relies on the prospective consideration of actions and their outcomes, which can be captured by forward-planning ‘model-based’ algorithms. So far, no studies have examined behavioral and neural signatures of model- free and model-based control in healthy high-impulsive individuals. Fifty healthy participants were drawn from the upper and lower ends of 452 individuals, completing the Barratt Impulsiveness Scale. All participants performed a sequential decision-making task during functional magnetic resonance imaging (fMRI) and underwent structural MRI. Behavioral and fMRI data were analyzed by means of computational algorithms reflecting model-free and model-based control. Both groups did not differ regarding the balance of model-free and model-based control, but high-impulsive individuals showed a subtle but significant accentuation of model-free control alone. Right lateral prefrontal model-based signatures were reduced in high-impulsive individuals. Effects of smoking, drinking, general cognition or gray matter density did not account for the findings. Irrespectively of impulsivity, gray matter density in the left dorsolateral prefrontal cortex was positively associated with model-based control. The present study supports the idea that high levels of impulsivity are accompanied by behavioral and neural signatures in favor of model-free behavioral control. Behavioral results in healthy high-impulsive individuals were qualitatively different to findings in patients with the same task. The predictive relevance of these results remains an important target for future longitudinal studies

Exchange between Escherichia coli polymerases II and III on a processivity clamp

Escherichia coli has three DNA polymerases implicated in the bypass of DNA damage, a process called translesion synthesis (TLS) that alleviates replication stalling. Although these polymerases are specialized for different DNA lesions, it is unclear if they interact differently with the replication machinery. Of the three, DNA polymerase (Pol) II remains the most enigmatic. Here we report a stable ternary complex of Pol II, the replicative polymerase Pol III core complex and the dimeric processivity clamp, β. Single-molecule experiments reveal that the interactions of Pol II and Pol III with β allow for rapid exchange during DNA synthesis. As with another TLS polymerase, Pol IV, increasing concentrations of Pol II displace the Pol III core during DNA synthesis in a minimal reconstitution of primer extension. However, in contrast to Pol IV, Pol II is inefficient at disrupting rolling-circle synthesis by the fully reconstituted Pol III replisome. Together, these data suggest a β-mediated mechanism of exchange between Pol II and Pol III that occurs outside the replication fork

Chronic depression: development and evaluation of the luebeck questionnaire for recording preoperational thinking (LQPT)

<p>Abstract</p> <p>Background</p> <p>A standardized instrument for recording the specific cognitive psychopathology of chronically depressed patients has not yet been developed. Up until now, preoperational thinking of chronically depressed patients has only been described in case studies, or through the external observations of therapists. The aim of this study was to develop and evaluate a standardized self-assessment instrument for measuring preoperational thinking that sufficiently conforms to the quality criteria for test theory.</p> <p>Methods</p> <p>The "Luebeck Questionnaire for Recording Preoperational Thinking (LQPT)" was developed and evaluated using a german sample consisting of 30 episodically depressed, 30 chronically depressed and 30 healthy volunteers. As an initial step the questionnaire was subjected to an item analysis and a final test form was compiled. In a second step, reliability and validity tests were performed.</p> <p>Results</p> <p>Overall, the results of this study showed that the LQPT is a useful, reliable and valid instrument. The reliability (split-half reliability 0.885; internal consistency 0.901) and the correlations with other instruments for measuring related constructs (control beliefs, interpersonal problems, stress management) proved to be satisfactory. Chronically depressed patients, episodically depressed patients and healthy volunteers could be distinguished from one another in a statistically significant manner (p < 0.001).</p> <p>Conclusion</p> <p>The questionnaire fulfilled the classical test quality criteria. With the LQPT there is an opportunity to test the theory underlying the CBASP model.</p

SOX2 is an amplified lineage-survival oncogene in lung and esophageal squamous cell carcinomas

Lineage survival oncogenes are activated by somatic DNA alterations in cancers arising from the cell lineages in which these genes play a role in normal development.1,2 Here we show that a peak of genomic amplification on chromosome 3q26.33, found in squamous cell carcinomas (SCCs) of the lung and esophagus, contains the transcription factor gene SOX2—which is mutated in hereditary human esophageal malformations3 and necessary for normal esophageal squamous development4, promotes differentiation and proliferation of basal tracheal cells5 and co-operates in induction of pluripotent stem cells.6,7,8 SOX2 expression is required for proliferation and anchorage-independent growth of lung and esophageal cell lines, as shown by RNA interference experiments. Furthermore, ectopic expression of SOX2 cooperated with FOXE1 or FGFR2 to transform immortalized tracheobronchial epithelial cells. SOX2-driven tumors show expression of markers of both squamous differentiation and pluripotency. These observations identify SOX2 as a novel lineage survival oncogene in lung and esophageal SCC

Gate pulsed readout of floating gate fet gas sensors

AbstractFloating gate FET (FGFET) gas sensors based on work function readout allow using a wide range of materials to be included as sensing materials. Longterm stability of the FGFET signal is influenced by unintended surface conductivity. A novel active operation mode presented in this work uses voltage pulses at the suspended gate to increase baseline stability and selectivity. This transient readout strategy allows differentiation between capacitive, volume-based effects and surface-located response, yielding two physically independent readout signals. Using this readout, the baseline stability as well as the selectivity for e.g. a FGFETbased humidity sensor can be increased significantly for polymeric and porous isolating sensing layers

Self-diffusion of particles interacting through a square-well or square-shoulder potential

The diffusion coefficient and velocity autocorrelation function for a fluid of particles interacting through a square-well or square-shoulder potential are calculated from a kinetic theory similar to the Davis-Rice-Sengers theory and the results are compared to those of computer simulations. At low densities the theory yields too low estimates due to the neglect of correlations between subsequent partial collisions of identical pairs; in particular, the neglect of boundstate effects appears important. At intermediate densities the theory makes reasonable predictions and at high densities it produces too high values, due to the neglect of ring terms and other correlated collision events. The results for the square-shoulder potential generally exhibit better agreement between theory and simulations than do those for the square-well potential

Risk factors for addiction and their association with model-based behavioral control

Addiction shows familial aggregation and previous endophenotype research suggests that healthy relatives of addicted individuals share altered behavioral and cognitive characteristics with individuals suffering from addiction. In this study we asked whether impairments in behavioral control proposed for addiction, namely a shift from goal-directed, model-based toward habitual, model-free control, extends toward an unaffected sample (n = 20) of adult children of alcohol-dependent fathers as compared to a sample without any personal or family history of alcohol addiction (n = 17). Using a sequential decision-making task designed to investigate model-free and model-based control combined with a computational modeling analysis, we did not find any evidence for altered behavioral control in individuals with a positive family history of alcohol addiction. Independent of family history of alcohol dependence, we however observed that the interaction of two different risk factors of addiction, namely impulsivity and cognitive capacities, predicts the balance of model-free and model-based behavioral control. Post-hoc tests showed a positive association of model-based behavior with cognitive capacity in the lower, but not in the higher impulsive group of the original sample. In an independent sample of particularly high- vs. low-impulsive individuals, we confirmed the interaction effect of cognitive capacities and high vs. low impulsivity on model-based control. In the confirmation sample, a positive association of omega with cognitive capacity was observed in highly impulsive individuals, but not in low impulsive individuals. Due to the moderate sample size of the study, further investigation of the association of risk factors for addiction with model-based behavior in larger sample sizes is warranted