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Most research on human fear conditioning and its generalization has focused on adults whereas only little is known about these processes in children. Direct comparisons between child and adult populations are needed to determine developmental risk markers of fear and anxiety. We compared 267 children and 285 adults in a differential fear conditioning paradigm and generalization test. Skin conductance responses (SCR) and ratings of valence and arousal were obtained to indicate fear learning. Both groups displayed robust and similar differential conditioning on subjective and physiological levels. However, children showed heightened fear generalization compared to adults as indexed by higher arousal ratings and SCR to the generalization stimuli. Results indicate overgeneralization of conditioned fear as a developmental correlate of fear learning. The developmental change from a shallow to a steeper generalization gradient is likely related to the maturation of brain structures that modulate efficient discrimination between danger and (ambiguous) safety cues.
Maintenance of hematopoietic stem cells and their potential to give rise to progenitors of differentiated lymphoid and myeloid cells are accomplished by a network of regulatory processes. As a part of this network, the heteromeric transcription factor GA-binding protein (GABP) plays a crucial role in self-renewal of murine hematopoietic and leukemic stem cells. Here, we report the consequences of functional impairment of GABP in human hematopoietic and in leukemic stem/progenitor cells. Ectopic overexpression of a dominant-negative acting GABP mutant led to impaired myeloid differentiation of CD34\(^{+}\) hematopoietic stem/progenitor cells obtained from healthy donors. Moreover, drastically reduced clonogenic capacity of leukemic stem/progenitor cells isolated from bone marrow aspirates of chronic myeloid leukemia (CML) patients underlines the importance of GABP on stem/progenitor cell maintenance and confirms the relevance of GABP for human myelopoiesis in healthy and diseased states.
Background
Direct interaction between Red blood cells (RBCs) and platelets is known for a long time. The bleeding time is prolonged in anemic patients independent of their platelet count and could be corrected by transfusion of RBCs, which indicates that RBCs play an important role in hemostasis and platelet activation. However, in the last few years, opposing mechanisms of platelet inhibition by RBCs derived nitric oxide (NO) were proposed. The aim of our study was to identify whether RBCs could produce NO and activate soluble guanylate cyclase (sGC) in platelets.
Methods
To test whether RBCs could activate sGC under different conditions (whole blood, under hypoxia, or even loaded with NO), we used our well-established and highly sensitive models of NO-dependent sGC activation in platelets and activation of purified sGC. The activation of sGC was monitored by detecting the phosphorylation of Vasodilator Stimulated Phosphoprotein (VASPS239) by flow cytometry and Western blot. ANOVA followed by Bonferroni’s test and Student’s t-test were used as appropriate.
Results
We show that in the whole blood, RBCs prevent NO-mediated inhibition of ADP and TRAP6-induced platelet activation. Likewise, coincubation of RBCs with platelets results in strong inhibition of NO-induced sGC activation. Under hypoxic conditions, incubation of RBCs with NO donor leads to Hb-NO formation which inhibits sGC activation in platelets. Similarly, RBCs inhibit activation of purified sGC, even under conditions optimal for RBC-mediated generation of NO from nitrite.
Conclusions
All our experiments demonstrate that RBCs act as strong NO scavengers and prevent NO-mediated inhibition of activated platelets. In all tested conditions, RBCs were not able to activate platelet or purified sGC.
Unaufhörliches Suchen – Gaddas Roman Quer pasticciaccio brutto de via Merulana als carmen perpetuum
(2016)
Gadda’s novel Quer Pasticciaccio brutto de Via Merulana tells the tale of two crimes committed in Rome in the 1920s. The search for the perpetrators turns into a pasticciaccio brutto (an awful mess), challenging the reader with its linguistic complexity and a myriad of references to history and culture; the large number of allusions to antiquity is particularly striking. References to Virgil’s Aeneid and to Rome’s mythical past do not constitute a mere transfer, but document a creative approach of transformational nature. Deformation and inversion are part of this process, changing the μορφή not only in formal terms, but also within the plot itself. These transformations of both form and content are read as Metamorphoses and analysed in comparison to Ovid’s homonymous work. The perpetual, never-ending quest for truth in Gadda’s novel necessitates a perpetual, never-ending narrative, which is conceptually related to Ovid’s carmen perpetuum.
The present study is concerned with a critical discourse analysis of the speeches of the Italian politicians Silvio Berlusconi and Matteo Renzi in different situations. The aim of the study was to find out how historical and speech contexts influence discourse structures and argumentations, and if any similar speech patterns or speech strategies were used. The results show that both politicians in many cases tend to utilize similar speech patterns to achieve different aims; each of them shows a preference for particular words, structures and strategies. It is noteworthy that one of the important differences between speeches of Berlusconi and Renzi is the use of various speech strategies. While Renzi uses these strategies to create an image of himself as a young and honest politician, Berlusconi makes use of them to defend himself or attack his opponents.
This article deals with the reception of Dante and Goethe in Ermanno Wolf-Ferrari’s and Hector Berlioz’s compositions La Vita Nuova and La Damnation de Faust. Although Dante Alighieri’s Vita Nova and Johann Wolfgang von Goethe’s Faust belong to completely different genres and epochs, the texts provide the basis for the oratorio-style works from the Romantic era, which justifies a comparative analysis of the latter. The examined reductions, extensions, modifications and rearrangements of the texts in the libretti – which were compiled almost entirely by the composers themselves – as well as the instrumental parts and the use and functions of the orchestra, the choir and the soloists, portray the intermedia relations between literature and music in the selected compositions. The chosen examples will show that the common idea of setting literature to music and the translation studies concept of intersemiotic translation are not appropriate for all literature-based pieces of music, as the analysis of both works demonstrates that with regard to vocal music a distinction should be made between the musicalization of literature and the literarization of music.
Economic, academic or artistic cooperation among actors of different countries or disciplines offers numerous new perspectives, but it also confronts the ones profiting from it with several challenges. First, identity has to be firmly established, which requires intercultural skills, such as role-distance, empathy and tolerance for ambiguities. Secondly, a third space is required in which meaning can be newly negotiated to make the partnership succeed. This paper proposes that even within one and the same language-group, one can speak of intercultural communication. A particular collaboration between Portuguese-speaking comic artists will be introduced, raising questions of the conditions necessary to make such a cooperation work. Answers will be provided according to the decisions the artists made in their publications.
In computer-supported learning environments, the deployment of self-regulatory skills represents an essential prerequisite for successful learning. Metacognitive prompts are a promising type of instructional support to activate students’ strategic learning activities. However, despite positive effects in previous studies, there are still a large number of students who do not benefit from provided support. Therefore, it may be necessary to consider explicitly the conditions under which a prompt is beneficial for a student, i.e., so-called adaptive scaffolding. The current study aims to (i) classify the effectiveness of prompts on regulatory behavior, (ii) investigate the correspondence of the classification with learning outcome, and (iii) discover the conditions under which prompts induce regulatory activities (i.e., the proper temporal positioning of prompts). The think-aloud data of an experiment in which metacognitive prompts supported the experimental group (n = 35) was used to distinguish between effective and non-effective prompts. Students’ activities preceding the prompt presentation were analyzed using data mining and process mining techniques. The results indicate that approximately half of the presented prompts induced metacognitive learning activities as expected. Moreover, the number of induced monitoring activities correlates positively with transfer performance. Finally, the occurrence of orientation and monitoring activities, which are not well-embedded in the course of learning, increases the effectiveness of a presented prompt. In general, our findings demonstrate the benefits of investigating metacognitive support using process data, which can provide implications for the design of effective instructional support.
Frank-Rutger Hausmann war Professor für Romanische Philologie (Schwerpunkt französische und italienische Literatur) in Freiburg, Aachen und wiederum Freiburg. Hausmann hat sich zudem intensiv mit der Fachgeschichte der deutschen Romanistik und der Geisteswissenschaften allgemein beschäftigt. Für die zweite Ausgabe der promptus-Interviewreihe durften wir ihn nach seiner Perspektive auf die historische und aktuelle Situation der Romanistik befragen. Er arbeitet momentan u.a. an einem Romanistenlexikon, das online veröffentlicht wird, und hat das Romanistenarchiv in Augsburg gegründet.
Die Zeitschrift promptus – Würzburger Beiträge zur Romanistik richtet sich an alle NachwuchswissenschaftlerInnen im Bereich der romanistischen Sprach- und Literaturwissenschaft sowie der Fachdidaktik. Das Ziel der Zeitschrift ist die Förderung der romanistischen Forschung im Allgemeinen und des wissenschaftlichen Nachwuchses der Romanistik im Besonderen. Sie versteht sich damit als Impulsgeber für junge romanistische Forschung, ohne sich dabei thematisch zu beschränken.
Genetic Dissection of Aversive Associative Olfactory Learning and Memory in Drosophila Larvae
(2016)
Memory formation is a highly complex and dynamic process. It consists of different phases, which depend on various neuronal and molecular mechanisms. In adult Drosophila it was shown that memory formation after aversive Pavlovian conditioning includes—besides other forms—a labile short-term component that consolidates within hours to a longer-lasting memory. Accordingly, memory formation requires the timely controlled action of different neuronal circuits, neurotransmitters, neuromodulators and molecules that were initially identified by classical forward genetic approaches. Compared to adult Drosophila, memory formation was only sporadically analyzed at its larval stage. Here we deconstruct the larval mnemonic organization after aversive olfactory conditioning. We show that after odor-high salt conditioning larvae form two parallel memory phases; a short lasting component that depends on cyclic adenosine 3’5’-monophosphate (cAMP) signaling and synapsin gene function. In addition, we show for the first time for Drosophila larvae an anesthesia resistant component, which relies on radish and bruchpilot gene function, protein kinase C activity, requires presynaptic output of mushroom body Kenyon cells and dopamine function. Given the numerical simplicity of the larval nervous system this work offers a unique prospect for studying memory formation of defined specifications, at full-brain scope with single-cell, and single-synapse resolution.
The transcriptional coactivator Bob1 promotes the development of follicular T helper cells via Bcl6
(2016)
Follicular T helper (Tfh) cells are key regulators of the germinal center reaction and long-term humoral immunity. Tfh cell differentiation requires the sustained expression of the transcriptional repressor Bcl6; however, its regulation in CD4\(^+\) T cells is incompletely understood. Here, we report that the transcriptional coactivator Bob1, encoded by the Pou2af1 gene, promotes Bcl6 expression and Tfh cell development. We found that Bob1 together with the octamer transcription factors Oct1/Oct2 can directly bind to and transactivate the Bcl6 and Btla promoters. Mixed bone marrow chimeras revealed that Bob1 is required for the expression of normal levels of Bcl6 and BTLA, thereby controlling the pool size and composition of the Tfh compartment in a T cell-intrinsic manner. Our data indicate that T cell-expressed Bob1 is directly involved in Tfh cell differentiation and required for mounting normal T cell-dependent B-cell responses.
This paper provides an overview of current progress in the technological advances and the use of deep brain stimulation (DBS) to treat neurological and neuropsychiatric disorders, as presented by participants of the Fourth Annual DBS Think Tank, which was convened in March 2016 in conjunction with the Center for Movement Disorders and Neurorestoration at the University of Florida, Gainesveille FL, USA. The Think Tank discussions first focused on policy and advocacy in DBS research and clinical practice, formation of registries, and issues involving the use of DBS in the treatment of Tourette Syndrome. Next, advances in the use of neuroimaging and electrochemical markers to enhance DBS specificity were addressed. Updates on ongoing use and developments of DBS for the treatment of Parkinson's disease, essential tremor, Alzheimer's disease, depression, post-traumatic stress disorder, obesity, addiction were presented, and progress toward innovation(s) in closed-loop applications were discussed. Each section of these proceedings provides updates and highlights of new information as presented at this year's international Think Tank, with a view toward current and near future advancement of the field.
Aims: We set out to investigate the antibacterial activity of a new Mn-based photoactivated carbon monoxide-releasing molecule (PhotoCORM, [Mn(CO)\(_3\)(tpa-kappa\(^3\)N)]\(^+\)) against an antibiotic-resistant uropathogenic strain (EC958) of Escherichia coli. Results: Activated PhotoCORM inhibits growth and decreases viability of E. coli EC958, but non-illuminated carbon monoxide-releasing molecule (CORM) is without effect. NADH-supported respiration rates are significantly decreased by activated PhotoCORM, mimicking the effect of dissolved CO gas. CO from the PhotoCORM binds to intracellular targets, namely respiratory oxidases in strain EC958 and a bacterial globin heterologously expressed in strain K-12. However, unlike previously characterized CORMs, the PhotoCORM is not significantly accumulated in cells, as deduced from the cellular manganese content. Activated PhotoCORM reacts avidly with hydrogen peroxide producing hydroxyl radicals; the observed peroxide-enhanced toxicity of the PhotoCORM is ameliorated by thiourea. The PhotoCORM also potentiates the effect of the antibiotic, doxycycline. Innovation: The present work investigates for the first time the antimicrobial activity of a light-activated PhotoCORM against an antibiotic-resistant pathogen. A comprehensive study of the effects of the PhotoCORM and its derivative molecules upon illumination is performed and mechanisms of toxicity of the activated PhotoCORM are investigated. Conclusion: The PhotoCORM allows a site-specific and time-controlled release of CO in bacterial cultures and has the potential to provide much needed information on the generality of CORM activities in biology. Understanding the mechanism(s) of activated PhotoCORM toxicity will be key in exploring the potential of this and similar compounds as antimicrobial agents, perhaps in combinatorial therapies with other agents.
Endogenous Testosterone and Exogenous Oxytocin Modulate Attentional Processing of Infant Faces
(2016)
Evidence indicates that hormones modulate the intensity of maternal care. Oxytocin is known for its positive influence on maternal behavior and its important role for childbirth. In contrast, testosterone promotes egocentric choices and reduces empathy. Further, testosterone decreases during parenthood which could be an adaptation to increased parental investment. The present study investigated the interaction between testosterone and oxytocin in attentional control and their influence on attention to baby schema in women. Higher endogenous testosterone was expected to decrease selective attention to child portraits in a face-in-the-crowd-paradigm, while oxytocin was expected to counteract this effect. As predicted, women with higher salivary testosterone were slower in orienting attention to infant targets in the context of adult distractors. Interestingly, reaction times to infant and adult stimuli decreased after oxytocin administration, but only in women with high endogenous testosterone. These results suggest that oxytocin may counteract the adverse effects of testosterone on a central aspect of social behavior and maternal caretaking.