Heritable factors account for approximately 40-60% of the total variance of liability to alcohol dependence. The present study tested whether a novel functional polymorphism in the promotor region of ...the X-chromosomal monoamine oxidase A gene (MAOA) was related to antisocial and anxious-depressive traits in alcoholics. Due to the X-chromosomal localization of the MAOA gene, psychobiological traits were compared separately for both genders of 298 male and 66 female alcoholics. In males, 30 of 59 alcoholics with antisocial personality disorder carried the low-activity 3-repeat allele in contrast to only 7 of 31 anxious-depressive alcoholics (51% vs. 23%; p = 0.02). Likewise, female anxious-depressive alcoholics showed a trend towards a low frequency of genotypes with the 3 repeat allele compared to female alcoholics without these symptoms (29% vs. 53%; p = 0.09). Taken together, these findings suggest that the 3-repeat allele of the MAOA polymorphism contributes modestly to the dimension of overand underreactive behaviors as possible antecedents of alcoholism.
Zusammenfassung
Das Aufmerksamkeitsdefizit-/Hyperaktivitätssyndrom (ADHS) ist eine klinisch heterogene Störung der Gehirnentwicklung unter Beteiligung zahlreicher genetischer und umweltbedingter ...Risikofaktoren. Ziel der interdisziplinär und translational ausgerichteten neurobiologischen Forschung ist, die wechselseitige Beziehung zwischen molekularen Mechanismen und strukturell-funktionellen Substraten in der Pathogenese des ADHS und ihre Bedeutung für den Langzeitverlauf der Erkrankung aufzuklären. Die Auseinandersetzung mit ADHS-spezifischen molekulargenetischen und entwicklungsbiologischen Grundlagen der Gehirnfunktion sowie strukturell-funktionellen Anlagen des Verhaltens verspricht, zur Entwicklung von Prädiktoren und differenziellen Strategien für die therapeutische Beeinflussung schwerer und chronischer Verläufe des ADHS beizutragen. Um evolutionär konservierte ADHS-relevante Prinzipien der Funktion und Struktur des Gehirns sowie des syndromtypischen Verhaltens zu definieren, ist ein integrierter Ansatz zur Aufklärung spezifischer neuro- und psychobiologischer Mechanismen und damit der systemischen Pathophysiologie des ADHS notwendig. Pathophysiologische Modelle des ADHS, insbesondere aber die syndromalen und komorbiden Dimensionen, benötigen daher die Kombination von molekulargenetischen, funktionell-bildgebenden, neuropsychologischen, verhaltensbiologischen und psychosozialen Strategien zur Erklärung vollständiger Kausalketten unter dem Gesichtspunkt einer gestörten Gehirnentwicklung.
This article represents the proceedings of a symposium presented at the 12th Congress of the International Society for Biomedical Research on Alcoholism held in Heidelberg/Mannheim, Germany, on ...October 1, 2004. The organizers and cochairs were Nassima Ait‐Daoud, MD, and Gerhard A. Wiesbeck, MD. The presentations included the following: (1) The Role of Nicotinic Acetylcholine Receptors in Alcohol‐Seeking Behavior, by Przemyslaw Bienkowski, MD, PhD; (2) Utilization of Linkage Analysis Combined with Microarray Technology to Identify Genes and Mechanisms Underlying Nicotine and Alcohol Use and Abuse in Humans and Rodents, by Ming D. Li, PhD; (3) Smoking and Alcoholic Chronic Pancreatitis: The Underestimated Risk?, by Roland H. Pfützer, MD; (4) Anticraving Medication in Alcohol and Nicotine Dependence, by Otto M. Lesch, MD, PhD; and (5) Pharmacotherapy for Promotion of Abstinence from Nicotine Among Alcohol‐Dependent Individuals, by Bankole A. Johnson, DSc, MD, PhD.
Objectives: To assess and compare the effectiveness of a simulation-based approach to change drivers' attitudes toward cellular phone use while driving for younger novice and older experienced ...drivers.
Methods: Thirty young novice drivers were tested on a driving simulator in this study. Their performance in dealing with driving tasks was measured for a single task and dual tasks (driving while using a cellular phone) and compared to 30 older experienced drivers tested previously in another study. Half of the younger drivers received video-based feedback regarding their performance in the two conditions, with an emphasis on the contribution of dual-tasking to degraded performance. The other half did not receive any performance feedback. Drivers' perceptions and attitudes toward cellular phone use while driving were investigated by a questionnaire before, immediately after, and again one month following the simulation-based testing for both groups of drivers (feedback; no feedback)
Results: All drivers (including the novice and experienced) reported willingness to engage in driving and talking on a cellular phone in some situations. The simulated driving test showed that a secondary cellular phone task significantly degraded driving performance for both the novice and the experienced drivers. The feedback treatment group (both the novice and the experienced) showed significant attitude change toward cellular phone use while driving (toward being less favorable), whereas the control group had no attitude change. At the one-month follow-up, the benefit of feedback was sustained more so in the experienced driver group than the novice driver group, although both groups still benefited relative to the control conditions.
Conclusions: Simulation-based feedback training is promising for short-term education in novice drivers but may be more effective in the long-term for drivers with higher levels of experience. Drivers with more experience appear to have a greater, more sustained benefit from the training than novices. Additional research is needed to better tailor this education method toward novice drivers. Impact: Simulation-based participative education approach through feedback needs to be better tailored toward novice drivers.
Converging evidence does not support GIT1 as an ADHD risk gene Klein, Marieke; van der Voet, Monique; Harich, Benjamin ...
American journal of medical genetics. Part B, Neuropsychiatric genetics,
September 2015, Letnik:
168B, Številka:
6
Journal Article
To probe the hypothesis of a role for a functionally relevant 44 bp insertion/deletion of the serotonin transporter promoter in the aetiopathogenesis of panic disorder, we determined the allele ...frequency of the variant in two samples (combined n = 158) of panic disorder patients (DSMIII-R) and compared it with its allele frequency in two ethnically matched control samples (combined n = 169). The fact that no difference could be observed (x 2 analysis) argues against a major role for this serotonin transporter promoter polymorphism in the aetiopathogenesis of panic disorder.
Drivers’ trust in an autonomous system Wright, Timothy J.; Horrey, William J.; Lesch, Mary F. ...
Proceedings of the Human Factors and Ergonomics Society Annual Meeting,
09/2016, Letnik:
60, Številka:
1
Journal Article
Recenzirano
Drivers’ trust in automation will likely determine the extent that autonomous and semi-autonomous vehicles are adopted, and once adopted, used properly. Unfortunately, previous studies have typically ...utilized overt subjective measures in determining an individual’s level of trust in automation. The current study aims to evaluate a covert behavioral measure of trust based on drivers’ body (head, hand, and foot) movements as they experience a simulated autonomous system. Videos of drivers interacting with an autonomous driving system in a driving simulator were coded. Body movement counts and average durations were derived from this coding and these data were compared across quartile rankings (based on self-reported trust) to examine body movements’ sensitivity to drivers’ level of trust. Results suggest body movements are not sensitive to individual differences in reported trust. Future work should further examine the utility of this covert behavioral metric by further examining situational differences.
Abstract
Systemic lupus erythematosus (SLE) is often considered a disease driven by autoreactive B cells and anti-nuclear antibodies. However, therapeutic targeting of B cells, for example through ...BAFF blockade, has been only partially effective in SLE. NF-kB Inducing Kinase (NIK) mediates non-canonical NF-kB signaling downstream of disease relevant TNF family members, such as BAFF, TWEAK, CD40, and OX40. We hypothesized that NIK inhibition might be more efficacious than BAFF blockade in lupus, and therefore generated a highly selective and potent small molecule inhibitor (SMI) of NIK to test this hypothesis. In cellular assays, this molecule inhibits non-canonical NF-kB signaling downstream of multiple TNFRSF family members. In order to differentiate the effects of NIK inhibition and BAFF blockade in vivo, we compared NIK inhibition with BAFF blockade in the context of NZB/W F1 lupus prone mice. As predicted, NIK inhibition recapitulated the pharmacological effects of BAFF blockade. Furthermore, NIK inhibition, but not BAFF blockade, affected T cell parameters in the spleen and pro-inflammatory gene expression in the kidney, the latter of which is partly attributable to TWEAK signaling. Finally, NIK inhibition resulted in improved survival, ameliorated renal pathology, and lower proteinuria scores. Collectively, our data suggest that NIK inhibition affects multiple disease-relevant pathways and may therefore have superior efficacy compared to BAFF inhibition in SLE.
The function of interleukin-18 (IL-18) was investigated in pertinent animal models of rodent rheumatoid arthritis (RA) to determine its proinflammatory and monocyte recruitment properties.
We used a ...modified Boyden chemotaxis system to examine monocyte recruitment to recombinant human (rhu) IL-18 in vitro. Monocyte recruitment to rhuIL-18 was then tested in vivo by using an RA synovial tissue (ST) severe combined immunodeficient (SCID) mouse chimera. We defined monocyte-specific signal-transduction pathways induced by rhuIL-18 with Western blotting analysis and linked this to in vitro monocyte chemotactic activity. Finally, the ability of IL-18 to induce a cytokine cascade during acute joint inflammatory responses was examined by inducing wild-type (Wt) and IL-18 gene-knockout mice with zymosan-induced arthritis (ZIA).
We found that intragraft injected rhuIL-18 was a robust monocyte recruitment factor to both human ST and regional (inguinal) murine lymph node (LN) tissue. IL-18 gene-knockout mice also showed pronounced reductions in joint inflammation during ZIA compared with Wt mice. Many proinflammatory cytokines were reduced in IL-18 gene-knockout mouse joint homogenates during ZIA, including macrophage inflammatory protein-3alpha (MIP-3alpha/CCL20), vascular endothelial cell growth factor (VEGF), and IL-17. Signal-transduction experiments revealed that IL-18 signals through p38 and ERK1/2 in monocytes, and that IL-18-mediated in vitro monocyte chemotaxis can be significantly inhibited by disruption of this pathway.
Our data suggest that IL-18 may be produced in acute inflammatory responses and support the notion that IL-18 may serve a hierarchic position for initiating joint inflammatory responses.
We present a scenario for efficient magnetization of very young galaxies about 0.5 gigayears after the Big-Bang by a cosmic ray-driven dynamo. These objects experience a phase of strong star ...formation during this first 109 years. We transfer the knowledge of the connection between star formation and the production rate of cosmic rays by supernova remnants to such high redshift objects. Since the supernova rate is a direct measure for the production rate of cosmic rays we conclude that very young galaxies must be strong sources of cosmic rays. The key argument of our model is the finding that magnetic fields and cosmic rays are dynamically coupled, i.e. a strong cosmic ray source contains strong magnetic fields since the relativistic particles drive an efficient dynamo in a galaxy via their buoyancy. We construct a phenomenological model of a dynamo driven by buoyancy of cosmic rays and show that if azimuthal shearing is strong enough the dynamo amplification timescale is close to the buoyancy timescale of the order of several $10^7 \div 10^8$ yr. We predict that young galaxies are strongly magnetized and may contribute significantly to the gamma-ray-background.
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