Die Funktion des Gap junction Proteins Innexin 2 im larvalen Proventrikulus von <em>Drosophila melanogaster</em>

Die direkte Kommunikation benachbarter Zellen durch Gap junctions ist notwendig für die Entwicklung von Geweben und Organen in Organismen. In Invertebraten setzen sich Gap junctions aus Proteinen der Innexinfamilie zusammen und bilden interzelluläre Kanäle, durch die die Zellen direkt metabolisch und elektrisch miteinander gekoppelt sind. Im Rahmen dieser Arbeit wurde die Bedeutung von Innexin 2 für die Etablierung der apikal-basal Polarität von Zellen in D. melanogaster detailliert untersucht. Die Untersuchungen konzentrierten sich dabei auf den Proventrikulus, da innexin 2 stark im Proventrikulus exprimiert ist und für die Ausbildung eines funktionellen Proventrikulus eine essentielle Bedeutung hat. In diesem Organ sind ebenfalls innexin 1 und 3 exprimiert. Koimmunpräzipitations-Experimente zeigten, dass Innexin 1 und 2 miteinander interagieren, wie auch schon für Innexin 2 und 3 nachgewiesen wurde. Diese Ergebnisse deuteten darauf hin, dass Innexine 1, 2 und 3 für eine effiziente Zell-Zell Kommunikation möglicherweise heteromere Kanäle ausbilden. Durch Farbkopplungsexperimente wurde nachgewiesen, dass in den kropf Mutanten die Zell-Zell Kommunikation stark beeinträchtigt ist. Übereinstimmend damit wurde durch in-situ-Hybridisierungs-Experimente und quantitative RT-PCR festgestellt, dass innexin 1 und 3 in der kropf Mutante auf transkriptioneller Ebene herunterreguliert sind. Die phänotypische Analyse des Proventrikulus in der kropf Mutante zeigte schwere Polaritätsdefekte. Durch ultrastrukturelle Untersuchungen des Proventrikulus mit Hilfe der Elektronenmikroskopie wurde festgestellt, dass besonders der apikale Bereich der Zellen betroffen ist. Weiterführende immunhistochemische Analysen des subapikalen Komlexes, welcher aus dem Crumbs- und dem Bazooka-Komplex besteht, identifizierten Bazooka und DaPKC als Komponenten des Bazooka-Komplexes, die in den kropf Mutanten fehllokalisiert sind. Zur Analyse der Ursache für die Fehllokalisation wurde der direkte Einfluss von Innexin 2 durch verschiedene Funktionsgewinn-Experimente untersucht. Dabei konnte nachgewiesen werden, dass die zelluläre Lokalisation von Bazooka vom C-Terminus von Innexin 2 abhängt. Darüber hinaus zeigten biochemische Interaktionsstudien, dass Bazooka direkt oder indirekt mit Innexin 2 interagiert. Zusammenfassend hat diese Misslokalisierung von Bazooka in kropf Mutanten eine besondere Bedeutung, da es in der Etablierung der apikalen Identität eine Schlüsselrolle innehat. So zeigen diese Experimente zum ersten Mal einen möglichen Mechanismus, wie Gap junction Proteine über eine Positionierung und Stabilisierung von Bazooka die Etablierung der zellulären Polarität beeinflussen könnten

Maternal personality, social support, and changes in depressive, anxiety, and stress symptoms during pregnancy and after delivery: A prospective-longitudinal study

Background: The role of maternal personality and perceived social support for peripartum changes in psychopathological symptoms remains unresolved. Methods In a regional-epidemiological sample of 306 women, depressive, anxiety, and stress symptoms were assessed three times during pregnancy and three times after delivery with the 21-item version of the Depression Anxiety Stress Scale. In pregnancy, the Big Five personality traits and perceived social support were assessed with the short version of the Big Five Inventory and the Social Support Questionnaire. Results Multilevel analyses revealed that depressive (b= -0.055) and stress (b= -0.047) symptoms decreased from early to late pregnancy. After delivery, anxiety symptoms were lower (two months postpartum:b= -0.193;four/ 16 months postpartum:b= -0.274), but stress symptoms were higher (two months postpartum:b= 0.468;four/ 16 months postpartum:b= 0.320) than during pregnancy. Across the peripartum period, more conscientious and more extraverted women experienced lower depressive and stress symptoms (b= -0.147 to -0.177), and more emotionally stable women experienced lower depressive, anxiety, and stress symptoms (b= -0.294 to -0.415). More emotionally stable women more strongly increased in anxiety during pregnancy (b= 0.019), and more extraverted women less strongly increased in depression after delivery (b= -0.010). Moreover, peripartum depressive, anxiety, and stress symptoms were lower in women with higher perceived social support (b= -0.225 to -0.308). Conclusions: Less emotionally stable, less conscientious, and less extraverted women and women with lower perceived social support seem to be at increased risk for peripartum psychopathological symptoms and might thus particularly profit from targeted prevention

Prospective Associations of Lifetime Post-traumatic Stress Disorder and Birth-Related Traumatization With Maternal and Infant Outcomes

Objective: Many women experience traumatic events already prior to or during pregnancy, and delivery of a child may also be perceived as a traumatic event, especially in women with prior post-traumatic stress disorder (PTSD). Birth-related PTSD might be unique in several ways, and it seems important to distinguish between lifetime PTSD and birth-related traumatization in order to examine specific consequences for mother and child. This post-hoc analysis aims to prospectively examine the relation of both, lifetime PTSD (with/without interpersonal trauma) and birth-related traumatization (with/without postpartum depression) with specific maternal and infant outcomes. Methods: In the prospective-longitudinal Maternal in Relation to Infants' Development (MARI) study, N = 306 women were repeatedly assessed across the peripartum period. Maternal lifetime PTSD and birth-related traumatization were assessed with the Composite International Diagnostic Interview for women. Maternal health during the peripartum period (incl. birth experience, breastfeeding, anxiety, and depression) and infant outcomes (e.g., gestational age, birth weight, neuropsychological development, and regulatory disorders) were assessed via standardized diagnostic interviews, questionnaires, medical records, and standardized observations. Results: A history of lifetime PTSD prior to or during pregnancy was reported by 25 women who indicated a less favorable psycho-social situation (lower educational level, less social support, a higher rate of nicotine consumption during pregnancy). Lifetime PTSD was associated with pregnancy-related anxieties, traumatic birth experience, and anxiety and depressive disorders after delivery (and in case of interpersonal trauma additionally associated with infant feeding disorder). Compared to the reference group, women with birth-related traumatization (N = 35) indicated numerous adverse maternal and infant outcomes (e.g., child-related fears, sexual problems, impaired bonding). Birth-related traumatization and postpartum depression was additionally associated with infant feeding and sleeping problems. Conclusion: Findings suggest that both lifetime PTSD and birth-related traumatization are important for maternal and infant health outcomes across the peripartum period. Larger prospective studies are warranted. Implications: Women with lifetime PTSD and/or birth related traumatization should be closely monitored and supported. They may benefit from early targeted interventions to prevent traumatic birth experience, an escalation of psychopathology during the peripartum period, and adverse infant outcomes, which in turn may prevent transgenerational transmission of trauma in the long term.Peer Reviewe

The Wall: A mobile app to identify and store social events from a digital image using computer vision

Social events, promoted in print media using posters, flyers and banners often fail to attract an audience because we frequently forget the details of the event when we pass-by the promotion on the street. Smaller venues or artists often rely on low-cost, street-level marketing campaigns in areas of high foot traffic areas to develop interest in an event. These venues or artist are often without a budget for online marketing or have a target demographic outside the typical Social Media consumer which makes attracting an audience difficult. This project aimed to solve the problem of storing and reminding the user of upcoming events, advertised in print media, by developing a mobile app to automatically identify and event information from an image taken by the user. The project is an N-tier system comprising: a front-end using AngularJS, Ionic and Cordova; a cloud Firebase database to store the user\u27s registration and logon credentials; Google Vision API to automatically segment and identify event information and the Google Calendar API to store and remind the user of upcoming events. The project was managed using the Agile Development methodology Scrum. The challenge of this project was in developing a solution to automatically and reliably identify event information from print media which often contains a wide variety of layouts, orientations, font types, colours and contrast variations between the information and any graphics present. In addition, the solution needed to understand the semantics of the text relating to the event name and location. The development frameworks and APIs chosen were unfamiliar to the team but were used because of their technical suitability and their ongoing and increasing popularity in the industry. Functional testing was based on a set of over 50 test images. Testing concluded that the solution retrieves date and time information consistently, however, more work is required to successfully segment and recognise event location and title. User Experience (UX) was measured in a cross-sectional survey of 75 participants. The results were positive and are discussed here

Neuroinflammation by cytotoxic T-lymphocytes impairs retrograde axonal transport in an oligodendrocyte mutant mouse

Mice overexpressing proteolipid protein (PLP) develop a leukodystrophy-like disease involving cytotoxic, CD8+ T-lymphocytes. Here we show that these cytotoxic T-lymphocytes perturb retrograde axonal transport. Using fluorogold stereotactically injected into the colliculus superior, we found that PLP overexpression in oligodendrocytes led to significantly reduced retrograde axonal transport in retina ganglion cell axons. We also observed an accumulation of mitochondria in the juxtaparanodal axonal swellings, indicative for a disturbed axonal transport. PLP overexpression in the absence of T-lymphocytes rescued retrograde axonal transport defects and abolished axonal swellings. Bone marrow transfer from wildtype mice, but not from perforin- or granzyme B-deficient mutants, into lymphocyte-deficient PLP mutant mice led again to impaired axonal transport and the formation of axonal swellings, which are predominantly located at the juxtaparanodal region. This demonstrates that the adaptive immune system, including cytotoxic T-lymphocytes which release perforin and granzyme B, are necessary to perturb axonal integrity in the PLP-transgenic disease model. Based on our observations, so far not attended molecular and cellular players belonging to the immune system should be considered to understand pathogenesis in inherited myelin disorders with progressive axonal damage

Reduced pain perception in children and adolescents with ADHD is normalized by methylphenidate

Background: The present study examined pain perception in children and adolescents with ADHD and the interaction between pain perception and the administration of methylphenidate (MPH) in order to generate hypotheses for further research that will help to clarify the association between ADHD diagnosis, MPH treatment and pain perception. Methods: We included 260 children and adolescents of the “German Health Interview and Examination Survey for Children and Adolescents” (KiGGS) and analyzed parent’s assessments of children’s pain distribution and pain perception, as well as the influence of MPH administration on pain perception in affected children and adolescents. Results: Pain perception was associated with ADHD and MPH administration, indicating that children and adolescents suffering from ADHD without MPH treatment were reported to have lower pain perception compared to both, healthy controls (HC) and ADHD patients medicated with MPH. Conclusion: We suggest that reduced pain perception in children and adolescents with ADHD not medicated with MPH may lead to higher risk tolerance by misjudgments of dangerous situations, expanding the importance of MPH administration in affected children and adolescents