Charakterisierung der monozytären Adhärenz bei myokardialer Ischämie und Reperfusionsschaden

Der akute Myokardinfarkt ist eine Erkrankung mit hoher Morbidität und Letalität. Ein überlebter Infarkt führt häufig zu Herzinsuffizienz, welche die Lebensqualität der Patienten deutlich eingeschränkt. In der vorliegenden Arbeit wird deshalb untersucht, ob therapeutisch in die Interaktion des Proteins Cyclophilin A (CyPA) mit seinem Rezeptor CD147 eingegriffen werden kann, um die Größe eines Herzinfarkts zu verringern. Dem zugrunde liegt die Hypothese, dass extrazelluläres CyPA über CD147 die Einwanderung von Monozyten in geschädigtes Myokard bewirkt. Dort führen Monozyten zu Zellschäden und einem Gewebeumbau, der die Entstehung einer Herzinsuffizienz begünstigt. In vivo wurde daher an Mäusen durch Ligatur der LAD ein Myokardinfarkt erzeugt und kurz vor der Reperfusion Antikörper gegen CD147 appliziert. In diesem praxisnahen Szenario wurden durch die Inhibition von CD147 sowohl die Infarktgröße als auch die Zahl einwandernder Zellen ins Infarktgebiet deutlich reduziert. In vitro wurde unter Strömungsbedingungen der Einfluss von CyPA auf das Adhäsionsverhalten monozytärer MonoMac6-Zellen an aktiviertem Endothel untersucht. Dabei konnte erstmals gezeigt werden, dass speziell extrazelluläres CyPA die monozytäre Adhäsion fördert. Es wurde nachgewiesen, dass dieser Effekt über den PI3K-Akt-Signalweg vermittelt wird. Die pharmakologische Inhibition von CyPA bzw. CD147 stellt damit einen vielversprechenden Ansatz für die zukünftige Therapie des Myokardinfarkts dar. Hierdurch könnte es gelingen, die Herzfunktion nach einem Infarkt langfristig zu verbessern. Da sowohl CyPA als auch CD147 v.a. bei Krankheitsprozessen exprimiert werden, ist ein geringes Nebenwirkungspotential wahrscheinlich, das durch die Fokussierung auf ausschließlich extrazelluläres CyPA weiter gesenkt werden kann. Das grundlegende Wissen um die Rolle des PI3K-Akt-Signalwegs bei der CyPA-vermittelten Monozytenadhäsion ermöglicht eine weitere Forschung, an deren Ende eine gezielte Beeinflussung intrazellulärer Signalwege in verschiedenen Krankheiten stehen könnte. In der vorliegenden Studie bleiben das höhere Alter der meisten Herzinfarkt-Patienten sowie häufige Komorbiditäten und Begleitmedikation unberücksichtigt. Daher müssen die Ergebnisse dieser Studie unter weiteren Bedingungen evaluiert werden, sodass es möglich wird, die Patienten zu identifizieren, welche von einer zusätzlichen Therapie durch CyPA-CD147-Inhibition profitieren

A problem case set for teaching psychophysics and psychophysical modeling

Psychophysics can be considered a methodological core for quantitative studies of perception, as well as attention, memory, decision making, etc. In typical introductory “Sensation and Perception” courses, students usually get a very basic idea of psychophysics and its main concepts. Here, I present an educational problem set for advanced practice in psychophysical data analysis and modeling. It is designed for students interested in a deeper understanding of perception and other cognitive processes and can be used as part of advanced undergraduate and master courses. Each problem case from the set includes a pregenerated data set and a research question that the student should answer by creating a psychophysical model (or several alternative models) and testing it against the data. Importantly, a successful model requires not only basic modeling and coding skills but also encourages deeper understanding of the logic of the method and basic concepts used to interpret behavior in a psychophysical experiment. The article also presents a demonstration case with a detailed tutorial on its solution that can be useful for both students and instructors

Entities also require relational coding and binding

Commentary on: An Integrative Memory model of recollection and familiarity to understand memory deficits by Bastin, Besson, Simon, Delhaye, Geurten, Willems, & Salmon. Behavioral and Brain Sciences. Abstract: Although Bastin et al. propose a useful model for thinking about the structure of memory and memory deficits, their distinction between entities and relational encoding is incompatible with data showing that even individual objects – prototypical ‘entities’ – are made up of distinct features which require binding. Thus, ‘entity’ and ‘relational’ brain regions may need to solve fundamentally the same problems

Individual representations in visual working memory inherit ensemble properties

Prevailing theories of visual working memory assume that each encoded item is stored or forgotten as a separate unit independent from other items. Here, we show that items are not independent, and that the recalled orientation of an individual item is strongly influenced by the summary statistical representation of all items (ensemble representation). We find that not only is memory for an individual orientation substantially biased towards the mean orientation, but the precision of memory for an individual item also closely tracks the precision with which people store the mean orientation (which is, in turn, correlated with the physical range of orientations). Thus, individual items are reported more precisely when items on a trial are more similar. Moreover, the narrower the range of orientations present on a trial, the more participants appear to rely on the mean orientation as representative of all individuals. Our results suggest that the information about a set of items is represented hierarchically, and that ensemble information can be an important source of information to constrain uncertain information about individuals

Effects of item distinctiveness on the retrieval of objects and object-location bindings from visual working memory

Visual working memory (VWM) is prone to interference from stored items competing for its limited capacity. Distinctiveness or similarity of the items is acknowledged to affect this competition, such that poor item distinctiveness causes a failure to discriminate between items sharing common features. In three experiments, we studied how the distinctiveness of studied real-world objects (i.e., whether the objects belong to the same or different basic categories) affects the retrieval of objects themselves (simple recognition) and object-location conjunctions (information about which object was where in a display, cued recall). In Experiments 1 and 2, we found that distinctiveness did not affect memories for objects or for locations, but low-distinctive objects were more frequently reported at “swapped” locations that originally contained other objects, showing object-location memory swaps. In Experiment 3 we found that observers swapped the location of a tested object with another object from the same category more frequently than with any of the objects from another category. This suggests that more similar studied objects cause more retrieval competition in object-location judgments than in simple recognition. Additionally, we discuss a possible role of categorical labeling of locations that can support object-location retrieval when the studied objects are highly distinct

Effects of item distinctiveness on the retrieval of objects and object-location bindings from visual working memory

Visual working memory (VWM) is prone to interference from stored items competing for its limited capacity. These competitive interactions can arise from different sources. For example, one such source is poor item distinctiveness causing a failure to discriminate between items sharing common features. Another source of interference is imperfect binding, a problem of determining which of the remembered features belonged to which object or which item was in which location. In two experiments, we studied how the conceptual distinctiveness of real-world objects (i.e., whether the objects belong to the same or different basic categories) affects VWM for objects and object-location binding. In Experiment 1 and 2, we found that distinctiveness did not affect memory for object identities or for locations, but low-distinctive objects were more frequently reported at “swapped” locations that originally contained other objects. In Experiment 3 we found evidence that the effect of distinctiveness on the object-location swaps was due to the use of categorical information for binding. In particular, we found that observers swapped the location of a tested object with another object from the same category more frequently than with any of the objects from another category. This suggests that observers can use some coarse category-location information when objects are conceptually distinct. Taken together, our findings suggest that object distinction and object-location binding act upon different components of VWM

Independent storage of different features of real-world objects in long-term memory.

People can store thousands of real-world objects in visual long-term memory with high precision. But are these objects stored as unitary, bound entities, as often assumed, or as bundles of separable features? We tested this in two experiments. Participants memorized specific exemplars of real-world objects presented in a particular state (e.g., open/closed; full/empty; etc), and then were asked to recognize either which exemplars they had seen (e.g., I saw this coffee mug), or which exemplar-state conjunctions they had seen (e.g., I saw this coffee mug and it was full). Participants frequently committed ‘swap’ errors, misremembering which states went with which exemplars. Furthermore, participants were very good at remembering which exemplars they had seen independently of whether these items were presented in a new or old state. Thus, the features of real-world objects that support exemplar discrimination and state discrimination are not bound, suggesting visual objects are not unitary entities in memory