Human interleukin-13 activates the interleukin-4-dependent transcription factor NF-IL4 sharing a DNA binding motif with an interferon-γ-induced nuclear binding factor

AbstractThe effects of interleukin-13 (IL-13) and interleukin-4 (IL-4) on cellular functions were shown to be quite similar. We provide evidence that in monocytes as well as in T lymphocytes both IL-4 and IL- 13 activate the same recently identified transcription factor NF-IL4 which binds to the specific responsive element IL-4RE. In addition, we show that a nuclear factor activated by interferon-γ also interacts with the IL-4RE. It differs from NF-IL4 in the electrophoretic mobility of the complex with DNA, in its DNA-binding specificity and in the proteins interacting with the DNA sequence. Sensitivity against various enzyme inhibitors suggests that components of the signal transduction pathway are shared by all three cytokines

Traumatized German soldiers with moral injury – value-based cognitive-behavioral group therapy to treat war-related shame

IntroductionDuring deployment, soldiers are confronted with potentially morally injurious events. In many cases, these events violate their personal values and belief systems, resulting in feelings of anger, alienation, guilt, and shame. The psychological distress caused by such transgressions is defined as moral injury. It remains unclear to date, which therapeutic interventions are most appropriate for addressing this specific psychological condition. This study examines the effectiveness of value-based cognitive-behavioral group therapy combining elements of cognitive-behavioral therapy, acceptance and commitment therapy, spiritual care, and adaptive disclosure therapy.Materials and methodsThis controlled study uses the Compass of Shame Scale to assess symptom severity among participants both before and after a three-week inpatient group therapy regimen for moral injury. An intervention group (n = 45) was compared to a waiting-list control group (n = 40). A one-way between subjects ANOVA was conducted to determine the differences between the two measurement points in the intervention group compared to the control group. A positive ethics vote from the Humboldt University Berlin (Charité) was available (No.EA1/092/15).ResultsA significant difference was found on the shame-associated maladaptive strategies subscales of attack self (F (1, 83) = 5.942, p = 0.017, Cohen’s f = 0,27), withdrawal (F (1, 83) = 8.263, p = 0.005, Cohen’s f = 0,32), and attack others (F (1, 83) = 10.552, p = 0.002, Cohen’s f = 0,36) of the Compass of Shame Scale between the intervention group and the control group at the p < 0.05 level in the pre- and post-treatment (t1-t2) comparison.ConclusionThis study suggests that the special therapeutic focus in cognitive-behavioral group therapy can alter shame-based maladaptive coping behaviors in response to war-related moral injury. This study provides further evidence that therapeutic approaches – through fostering a reconciliatory, compassionate, and forgiving approach toward oneself and others – target the underlying mechanisms of moral injury. Therefore, value-based cognitive-behavioral interventions should be considered as a standard element of trauma care in a military setting. Future studies should further examine such interventions in randomized control trials. It would also be particularly valuable for future studies to include a follow-up time point

Chronic voluntary oral methamphetamine induces deficits in spatial learning and hippocampal protein kinase Mzeta with enhanced astrogliosis and cyclooxygenase-2 levels

Methamphetamine (MA) is an addictive drug with neurotoxic effects on the brain producing cognitive impairment and increasing the risk for neurodegenerative disease. Research has focused largely on examining the neurochemical and behavioral deficits induced by injecting relatively high doses of MA [30 mg/kg of body weight (bw)] identifying the upper limits of MA-induced neurotoxicity. Accordingly, we have developed an appetitive mouse model of voluntary oral MA administration (VOMA) based on the consumption of a palatable sweetened oatmeal mash containing a known amount of MA. This VOMA model is useful for determining the lower limits necessary to produce neurotoxicity in the short-term and long-term as it progresses over time. We show that mice consumed on average 1.743 mg/kg bw/hour during 3 hours, and an average of 5.23 mg/kg bw/day over 28 consecutive days on a VOMA schedule. Since this consumption rate is much lower than the neurotoxic doses typically injected, we assessed the effects of longterm chronic VOMA on both spatial memory performance and on the levels of neurotoxicity in the hippocampus. Following 28 days of VOMA, mice exhibited a significant deficit in short-term spatial working memory and spatial reference learning on the radial 8-arm maze (RAM) compared to controls. This was accompanied by a significant decrease in memory markers protein kinase Mzeta (PKMζ), calcium impermeable AMPA receptor subunit GluA2, and the postsynaptic density 95 (PSD-95) protein in the hippocampus. Compared to controls, the VOMA paradigm also induced decreases in hippocampal levels of dopamine transporter (DAT) and tyrosine hydroxylase (TH), as well as increases in dopamine 1 receptor (D1R), glial fibrillary acidic protein (GFAP) and cyclooxygenase-2 (COX-2), with a decrease in prostaglandins E2 (PGE2) and D2 (PGD2). These results demonstrate that chronic VOMA reaching 146 mg/kg bw/28d induces significant hippocampal neurotoxicity. Future studies will evaluate the progression of this neurotoxic state

The Posttraumatic Cognitions Inventory (PTCI) – Development and Validation of a Shortened Military Version Based on a Sample of German Soldiers with Deployment-Related Trauma

Alliger-Horn C, Hahn I, Hessenbruch I, et al. The Posttraumatic Cognitions Inventory (PTCI) – Development and Validation of a Shortened Military Version Based on a Sample of German Soldiers with Deployment-Related Trauma. Journal of Traumatic Stress Disorders & Treatment. 2017;6(2)

The BI'LF4 trans-activator of Epstein-Barr virus is modulated by type and differentiation of the host cell

We have analyzed the activity and regulated expression of a new Epstein-Barr virus (EBV) trans-activator (I'ta) encoded by left reading frame 4 (BI'LF4) of the BamHI I'fragment. The gene was detected in all genomes of established EBV strains and individual isolates, with the exception of B95-8, where the type-specific deletion of this open reading frame is tolerated in vitro. Specific trans-activation of two EBV promoters (early MS and I'ta promoter) could be shown in cotransfection assays. The I'ta product affected autoactivation but had no influence on heterologous target promoters. The I'ta promoter segment was shown to be costimulated in the process of host cell differentiation in the absence of other EBV gene products. Expression of the reading frame in bacteria identified a 48-kDa protein as a stable gene product. I'ta-specific antibodies were detected in sera from EBV-positive persons (nasopharyngeal carcinoma). When expressed with suitable eucaryotic vectors, a nuclear protein could be immunostained in transfected cells. Our experiments suggest a cell type-specific requirement for I'ta in the lytic cycle of EBV at a determined differentiation stage of the host cell

Chronic voluntary oral methamphetamine induces deficits in spatial learning and hippocampal protein kinase Mzeta with enhanced astrogliosis and cyclooxygenase-2 levels

Methamphetamine (MA) is an addictive drug with neurotoxic effects on the brain producing cognitive impairment and increasing the risk for neurodegenerative disease. Research has focused largely on examining the neurochemical and behavioral deficits induced by injecting relatively high doses of MA [30 mg/kg of body weight (bw)] identifying the upper limits of MA-induced neurotoxicity. Accordingly, we have developed an appetitive mouse model of voluntary oral MA administration (VOMA) based on the consumption of a palatable sweetened oatmeal mash containing a known amount of MA. This VOMA model is useful for determining the lower limits necessary to produce neurotoxicity in the short-term and long-term as it progresses over time. We show that mice consumed on average 1.743 mg/kg bw/hour during 3 hours, and an average of 5.23 mg/kg bw/day over 28 consecutive days on a VOMA schedule. Since this consumption rate is much lower than the neurotoxic doses typically injected, we assessed the effects of long-term chronic VOMA on both spatial memory performance and on the levels of neurotoxicity in the hippocampus. Following 28 days of VOMA, mice exhibited a significant deficit in short-term spatial working memory and spatial reference learning on the radial 8-arm maze (RAM) compared to controls. This was accompanied by a significant decrease in memory markers protein kinase Mzeta (PKMζ), calcium impermeable AMPA receptor subunit GluA2, and the post-synaptic density 95 (PSD-95) protein in the hippocampus. Compared to controls, the VOMA paradigm also induced decreases in hippocampal levels of dopamine transporter (DAT) and tyrosine hydroxylase (TH), as well as increases in dopamine 1 receptor (D1R), glial fibrillary acidic protein (GFAP) and cyclooxygenase-2 (COX-2), with a decrease in prostaglandins E2 (PGE2) and D2 (PGD2). These results demonstrate that chronic VOMA reaching 146 mg/kg bw/28d induces significant hippocampal neurotoxicity. Future studies will evaluate the progression of this neurotoxic state

Zusammenhänge zwischen Psychischer Symptomatik und Persönlichen Werten bei Bundeswehrsoldaten nach einem Auslandseinsatz

Ziel: Der Einfluss von Wertorientierungen ist bislang im militärischen Kontext nicht empirisch untersucht. Methodik: 117 Soldaten bearbeiteten nach Auslandseinsatz den Portrait-Values-Questionnaire, den Patient-Health-Questionnaire sowie die Resilienzskala-11. Ergebnisse: Hedonismus, Benevolenz, Tradition, Selbstbestimmung und Universalismus hatten einen in der Zusammensetzung jeweils differenten signifikanten Einfluss auf depressive, ängstliche und somatoforme Syndrome im PHQ. Die RS-11 korrelierte negativ mit der Symptomatik. Schlussfolgerung: Werteorientierungen und Resilienz sollten bei Soldaten nach Einsätzen vermehrt Beachtung finden. Objective: Soldiers are at increased risk of developing mental health disorders after military deployment. The impact of personal values on psychological symptomatology based on an empirical working model has not yet been studied in a military environment. Methods: 117 German Armed Forces soldiers completed the Portrait-Values-Questionnaire (PVQ), the Patient-Health-Questionnaire (PHQ) and the Resilience-Scale (RS-11) after their deployment to Afghanistan. Results: In the regression analyses the values hedonism, benevolence, tradition, self-direction and universalism had a differential significant impact on depression, anxiety and somatoform symptoms of the PHQ. The RS-11 sum scale values were negatively correlated with symptomatology. Conclusion: Personal values and resilience seem to be associated with psychological symptomatology in soldiers after military deployment. The results can contribute to the further development of both preventive and therapeutic approaches

Depressivität und Wert­orientierungen im Verlauf von militärischen Auslands­einsätzen

Zusammenfassung : Depressivität und andere psychische Erkrankungen sind eine häufige Begleiterscheinung militärischer Auslandseinsätze. Ein neueres Forschungsfeld befasst sich mit persönlichen Wert­orientierungen und moralischen Verletzungen und deren Rolle bei der Entstehung psychischer Einsatzfolgen. In der vorliegenden Studie wurden Bundeswehrsoldaten vor und unmittelbar nach einem Auslandseinsatz in Afghanistan im Hinblick auf Wertorientierungen, moralische Verletzungen, posttraumatische Symptomatik sowie Depressivität psychometrisch getestet und mit einer Kontrollgruppe ohne Auslandseinsatz verglichen. In der Einsatzgruppe veränderte sich das umfassende Wertebewusstsein (Wert­e­index) signifikant weniger als in der Kontroll­gruppe. Dieser Werteindex sowie auch die Werte Konformität und Tradition waren signifikant mit der Entwicklung von Depressivität in der Einsatzgruppe ­assoziiert. Wertorientierungen sollten zukünftig in der Einsatzvorbereitung von Soldaten, aber auch in der Therapie einsatzbezogener psychischer Erkrankungen vermehrt berücksichtigt werden. = Abstract : Depression and Value ­Orientation in the Course of Military ­Operations Abroad Depression and other psychic disorders are a common side effect of military missions abroad. A relatively new field of research investigates personal value orientations and moral injuries and inquires into the role they play in the onset of psycholo­gical problems following involvement in military operations. In the present study, German Bundeswehr soldiers were tested psychometrically before and immediately after a mission in Afghanistan for value orientations, moral injuries, posttraumatic symptoms and depression. They were compared with a control group that had not undergone a military assignment abroad. Value awareness (value index) changed significantly less in the task force than in the control group. Both this value index and the values «conformity« and «tradition« were significantly associated with the onset of depression in the task force. In future, value orientations should be given closer attention both in the preparation of soldiers for deployment and in therapy for psychic disorders associated with deployment