Schwingungsspektroskopische Untersuchungen zu zellulären Altersprozessen von humanen Fibroblastzellen

Um die Gesundheit bis ins hohe Alter zu gewährleisten, sind die alternsassoziierten Fehlfunktionen und Erkrankungen von Interesse. Ziel der Alternsforschung ist es, diese Mechanismen zu identifizieren und Ansatzpunkte zu gewinnen, die den Zustand des „gesunden“ Alterns verlängern können. Humane Zellen nehmen im Gewebe verschiedene Zellzustände ein. Neben der Proliferation können Zellen im Zellzyklus aufgrund exogener und endogener Stressoren arretieren. Unterschieden werden seneszente und quieszente Zellen, die durch einen irreversiblen bzw. reversiblen Zellzyklusarrest gekennzeichnet sind. Übergänge in andere Zellzustände werden dadurch verhindert. Jedoch beruhen die meisten Erkenntnisse zu zellulären Veränderungen auf zweidimensionalen (2D) Zellkultivierungen. Werden Zellen dagegen in einem dreidimensionalen (3D) Modell kultiviert, imitieren diese das Verhalten unter natürlichen Umgebungsbedingungen. Auch unterliegen die durch den Zellzyklusarrest gekennzeichneten Zellen ähnlichen Signalwegen. Dadurch treten gemeinsame Merkmale in quieszenten und seneszenten Zellen auf. Zudem beruht die Detektion dieser Zellen auf charakteristischen Biomarkern, die z. B. nicht einheitlich exprimiert werden. Auch sind bisherige Marker nicht ausreichend spezifisch und können die Zellzustände nicht eindeutig voneinander abgrenzen. Alternative Identifizierungsmethoden, die markierungsfrei, nicht-invasiv und in vivo einsetzbar sind, werden daher für die Alternsforschung benötigt. Die Schwingungsspektroskopie, wie die Raman- und Infrarot-Spektroskopie, werden daher als Analysetechniken in der hier vorliegenden Arbeit verwendet, um seneszente Zellen gegenüber proliferierenden bzw. quieszenten Zellen in 2D- bzw. 3D-Umgebungen zu untersuchen und abzugrenzen. Mit Hilfe multivariater Datenanalysen sollen Muster in den umfangreichen Datensätzen sowie feine spektrale Unterschiede sichtbar gemacht werden

What are the basic modules of implicit sequence learning? A feature-based account

According to the Theory of Event Coding (TEC; Hommel et al., 2001), action and perception are represented in a shared format in the cognitive system by means of feature codes. In implicit sequence learning research, it is still common to make a conceptual difference between independent motor and perceptual sequences. This supposedly independent learning takes place in encapsulated modules (Keele et al., 2003) which process information along single dimensions. These dimensions have remained underspecified so far. It is especially not clear whether stimulus- and response characteristics are processed in separate modules. In this thesis, it is suggested that features as they are described in the TEC should be viewed as the basic modules of implicit learning. This means that the modules process all stimulus- and response information related to a certain feature of the perceptual environment. By means of a serial reaction time task, the nature of the basic units of implicit learning will be investigated with the exemplary learning type of location sequence learning. In Experiments 1-3, it is shown that a stimulus location sequence and a response location sequence cannot be learnt without interference unless one of the sequences can be coded via an alternative, non-spatial dimension. These results support the notion that location is one module of the implicit learning system and consequently, that there are no separate processing units for stimulus locations vs. response locations. In Experiments 4 and 5, it is shown that learning of a stimulus location sequence can lead to facilitating transfer to a response location sequence relying on the same location feature codes. These findings give further evidence that inside an implicit learning module, all stimulus- and response information relying on the same feature code get simultaneously activated. Taken together, the experiments suggest that implicit learning processes rely on the same mechanisms postulated in the TEC (Hommel et al., 2001) for action coding on a trial-to-trial basis. Most importantly, stimulus- and response characteristics of a sequence are not processed or learnt independently from each other. This can lead to both interference and facilitation effects

Interventions to Promote Positive Affect and Physical Activity in Children, Adolescents and Young Adults—A Systematic Review

Interventions to promote physical activity (PA) in children, adolescents and young adults based on social-cognitive theories often fail to increase PA. In recent years, affect-based approaches have gained interest, but the current state of research is not sufficiently reported. Therefore, a systematic review about the influence of interventions to promote positive affect and PA enjoyment and PA in children, adolescents and young adults was conducted. Literature searches were carried out including studies published between September 2009 and April 2019. Intervention studies targeting healthy children, adolescents or young adults and measuring enjoyment and PA were included. Thirteen studies met the inclusion criteria, including five group-based PA interventions, three multi-component school interventions, two internet-based interventions and three exergaming interventions. Most studies use multiple components in their intervention. Group-based PA programs incorporating task-oriented teaching styles and opportunities for voluntary PA are most consistently associated with positive findings. This review shows moderate evidence of interventions for children, adolescents and young adults being effective in increasing enjoyment and PA. Besides physical education and comprehensive school interventions, heterogenous intervention designs limit the comparability of studies. Future research should focus on theory-based, multi-component interventions with mediator analyses

Pharmacological targeting of host chaperones protects from pertussis toxin in vitro and in vivo

Whooping cough is caused by Bordetella pertussis that releases pertussis toxin (PT) which comprises enzyme A-subunit PTS1 and binding/transport B-subunit. After receptor-mediated endocytosis, PT reaches the endoplasmic reticulum from where unfolded PTS1 is transported to the cytosol. PTS1 ADP-ribosylates G-protein alpha -subunits resulting in increased cAMP signaling. Here, a role of target cell chaperones Hsp90, Hsp70, cyclophilins and FK506-binding proteins for cytosolic PTS1-uptake is demonstrated. PTS1 specifically and directly interacts with chaperones in vitro and in cells. Specific pharmacological chaperone inhibition protects CHO-K1, human primary airway basal cells and a fully differentiated airway epithelium from PT-intoxication by reducing intracellular PTS1-amounts without affecting cell binding or enzyme activity. PT is internalized by human airway epithelium secretory but not ciliated cells and leads to increase of apical surface liquid. Cyclophilin-inhibitors reduced leukocytosis in infant mouse model of pertussis, indicating their promising potential for developing novel therapeutic strategies against whooping cough

Presolar grains from meteorites: Remnants from the early times of the solar system

This review provides an introduction to presolar grains - preserved stardust from the interstellar molecular cloud from which our solar system formed - found in primitive meteorites. We describe the search for the presolar components, the currently known presolar mineral populations, and the chemical and isotopic characteristics of the grains and dust-forming stars to identify the grains' most probable stellar sources. Keywords: presolar grains, interstellar dust, asymptotic giant branch (AGB) stars, novae, supernovae, nucleosynthesis, isotopic ratios, meteoritesComment: 71 pages, 24 figures, 9 tables. Invited review. to appear in Chemie der Erd

Abstract Feature Codes: The Building Blocks of the Implicit Learning System

According to the Theory of Event Coding (TEC; Hommel, Musseler, Aschersleben, & Prinz, 2001), action and perception are represented in a shared format in the cognitive system by means of feature codes. In implicit sequence learning research, it is still common to make a conceptual difference between independent motor and perceptual sequences. This supposedly independent learning takes place in encapsulated modules (Keele, Ivry, Mayr, Hazeltine, & Heuer 2003) that process information along single dimensions. These dimensions have remained underspecified so far. It is especially not clear whether stimulus and response characteristics are processed in separate modules. Here, we suggest that feature dimensions as they are described in the TEC should be viewed as the basic content of modules of implicit learning. This means that the modules process all stimulus and response information related to certain feature dimensions of the perceptual environment. In 3 experiments, we investigated by means of a serial reaction time task the nature of the basic units of implicit learning. As a test case, we used stimulus location sequence learning. The results show that a stimulus location sequence and a response location sequence cannot be learned without interference (Experiment 2) unless one of the sequences can be coded via an alternative, nonspatial dimension (Experiment 3). These results support the notion that spatial location is one module of the implicit learning system and, consequently, that there are no separate processing units for stimulus versus response locations

Feature codes in implicit sequence learning: perceived stimulus locations transfer to motor response locations

An important question in implicit sequence learning research is how the learned information is represented. In earlier models, the representations underlying implicit learning were viewed as being either purely motor or perceptual. These different conceptions were later integrated by multidimensional models such as the Dual System Model of Keele et al. (Psychol Rev 110(2):316-339, 2003). According to this model, different types of sequential information can be learned in parallel, as long as each sequence comprised only one single dimension (e.g., shapes, colors, or response locations). The term dimension, though, is underspecified as it remains an open question whether the involved learning modules are restricted to motor or to perceptual information. This study aims to show that the modules of the implicit learning system are not specific to motor or perceptual processing. Rather, each module processes an abstract feature code which represents both response- and perception-related information. In two experiments, we showed that perceiving a stimulus-location sequence transferred to a motor response-location sequence. This result shows that the mere perception of a sequential feature automatically leads to an activation of the respective motor feature, supporting the notion of abstract feature codes being the basic modules of the implicit learning system. This result could only be obtained, though, when the task instructions emphasized the encoding of the stimulus-locations as opposed to an encoding of the color features. This limitation will be discussed taking into account the importance of the instructed task set

Implicit visual learning: How the task set modulates learning by determining the stimulus-response binding

Implicit learning is one of the most fundamental learning mechanisms that enables humans to adapt to regularities inherent in the environment. Despite its high flexibility, it depends on constraints, such as selective attention. Here, we focused on the stimulus-to-response binding which defines the dimensions of the stimuli and the responses participants attend to. In a serial reaction time task with a visual sequence, we investigated whether this stimulus-response binding influences the amount of sequence learning. The results of Experiments 1 and 2 showed that visual sequence learning is reduced when participants do not attend to the relevant response dimension. Furthermore, the findings of Experiment 3 suggest that attention to the relevant response dimension increased the development of explicit knowledge without affecting implicit knowledge. This latter finding is difficult to reconcile with the assumption that explicit learning results from the gradual strengthening of sequence representations. (C) 2014 Elsevier Inc. All rights reserved

Raman and infrared spectroscopy reveal that proliferating and quiescent human fibroblast cells age by biochemically similar but not identical processes.

Dermal fibroblast cells can adopt different cell states such as proliferation, quiescence, apoptosis or senescence, in order to ensure tissue homeostasis. Proliferating (dividing) cells pass through the phases of the cell cycle, while quiescent and senescent cells exist in a non-proliferating cell cycle-arrested state. However, the reversible quiescence state is in contrast to the irreversible senescence state. Long-term quiescent cells transit into senescence indicating that cells age also when not passing through the cell cycle. Here, by label-free in vitro vibrational spectroscopy, we studied the biomolecular composition of quiescent dermal fibroblast cells and compared them with those of proliferating and senescent cells. Spectra were examined by multivariate statistical analysis using a PLS-LDA classification model, revealing differences in the biomolecular composition between the cell states mainly associated with protein alterations (variations in the side chain residues of amino acids and protein secondary structure), but also within nucleic acids and lipids. We observed spectral changes in quiescent compared to proliferating cells, which increased with quiescence cultivation time. Raman and infrared spectroscopy, which yield complementary biochemical information, clearly distinguished contact-inhibited from serum-starved quiescent cells. Furthermore, the spectra displayed spectral differences between quiescent cells and proliferating cells, which had recovered from quiescence. This became more distinct with increasing quiescence cultivation time. When comparing proliferating, (in particular long-term) quiescent and senescent cells, we found that Raman as well as infrared spectroscopy can separate these three cellular states from each other due to differences in their biomolecular composition. Our spectroscopic analysis shows that proliferating and quiescent fibroblast cells age by similar but biochemically not identical processes. Despite their aging induced changes, over long time periods quiescent cells can return into the cell cycle. Finally however, the cell cycle arrest becomes irreversible indicating senescence