Grain size effects in rime judgment across literacy development in German

Phonological similarity effects are biases to judge words as phonologically similar (i.e., rhyming), even if they are not. First found in rime awareness tasks in preliterates, these biases have recently also been found in proficient adult readers. In this study, we evaluated underlying phonological processing in rime judgment longitudinally, across literacy development. To this end, we created a new rime judgment task with two distractor conditions, that varied in size of phonological overlap. The task was administered to a group of 61 German speaking children at four time-points across school entry and to 21 adults. Accuracy and latency responses were recorded. Results showed that children and adults showed phonological similarity effects but the effect decreased gradually over time. However, preliterate children were more sensitive to large compared to small phonological overlap, while the same effect was significantly smaller in literate children and adults. Results suggests that preliterate children are more sensitive to larger grain sizes and become more sensitive to fine-grained units across literacy development. The findings are in line with the assumptions of the psycholinguistic grain size theory. (DIPF/Orig.

Interaktion gedächtnis- und erklärungs-basierter Verarbeitungsprozesse bei der pronominalen Auflösung. Analyse der Effekte von Impliziten Kausalitäts- und Gender-Informationen durch die Modellierung von Reaktionszeitverteilungen.

In der aktuellen sprachpsychologischen Forschung werden zwei divergierende Erklärungsmodelle für die pronominale Auflösung vertreten: Sog. gedächtnis-basierte Ansätze konzeptualisieren sie als einen allgemeinen, automatischen Prozess der Gedächtnissuche. Das Pronomen fungiert als Abruf-Cue und alle Elemente im Langzeitspeicher werden vom Cue in Abhängigkeit vom Grad der Merkmalsüberlappung aktiviert. Erklärungs-basierte Ansätze modellieren die pronominale Auflösung hingegen als einen kontrollierten, quasi-syllogistischen Schlussprozess, in dem sich die Belegung der freien Pronomen-Variable aus einer zugrunde liegenden Prämisse ableitet. Anhand einer Analyse der komplexen Effekte von Impliziten Kausalitäts-(IC) und Gender-Informationen auf die pronominale Auflösung wird in der vorliegenden Arbeit gezeigt, dass sowohl gedächtnis- als auch erklärungs-basierte Prozesse an der Referenzzuweisung beteiligt sind und dynamisch miteinander interagieren. Das Konstrukt der impliziten Verbkausalität bezieht sich dabei auf die Tatsache, dass bestimmte (transitive) Verben ihr kausales Gewicht entweder auf das Satz-Subjekt oder das -Objekt legen (z.B. "fürchten" vs. "ängstigen"). Man findet konsistent, dass ein nachfolgendes Pronomen bevorzugt in Richtung des kausal salienten Aktanten aufgelöst wird und inkongruente Auflösungen schwerer zu verarbeiten sind (sog. IC-Erleichterungseffekt). Zur Erklärung dieses Phänomens werden in der Literatur zwei Hypothesen kontrastiert: Die sog. Fokussierungs-Hypothese nimmt an, dass die implizite Verbkausalität zu einer direkten, gedächtnis-basierten Voraktivierung des kongruenten Referenten führt. Die sog. Integrations-Hypothese behauptet hingegen, dass inkongruente Auflösungen satzfinal mittels einer erklärungs-basierten Zusatzinferenz in das Diskursmodell integriert werden. Für die Effekte der Genus-Kongruenz von Pronomen und Antezedens werden in der Literatur zwei sehr ähnliche Erklärungsmodelle vertreten (gedächtnis-basierte confirmation- vs. erklärungs-basierte disengagement-Hypothese). In der vorliegenden Arbeit wird dafür argumentiert, dass sich die verschiedenen Hypothesen nicht gegenseitig ausschließen, sondern vielmehr wechselseitig ergänzen: Frühe gedächtnis-basierte Verarbeitungsprozesse bereiten die pronominale Auflösung vor, die Plausibilität der letztendlichen Referenzzuweisung muss jedoch abschließend mittels erklärungs-basierter Verarbeitungsprozesse evaluiert werden. Speziell wird für die implizite Verbkausalität eine trade-off-Relation von früher Refokussierungs- und spätem Integrationsaufwand angenommen: Wenn die pronominale Auflösung bereits durch gedächtnis-basierte Fokussierungs-Prozesse optimal vorbereitet ist, dann verringert sich der spätere Integrationsaufwand. Eine frühe Refokussierung ist allerdings nur dann möglich, wenn disambiguierende Genus-Informationen vorhanden sind, welche die Diskrepanz von Voraktivierung und Diskursmodell früh indizieren und damit eine direkte Reanalyse ermöglichen. Zur Überprüfung dieses Modells wurde die Methode der Reaktionszeit-Verteilungsanalyse herangezogen. Bei dieser werden durch die gleichzeitige Erfassung unterschiedlicher Charakteristika einer Reaktionszeitverteilung Prozessindikatoren für unterschiedliche kognitive Operationen extrahiert. Konkret wurde die Weibull-Verteilung als parametrisches Modell verwendet und der Lokations-Parameter als Indikator für die hierarchie-niedrigen, der Skalierungs-Parameter als Indikator für das Ausmaß an hierarchie-hoher Verarbeitung interpretiert. Das Modell wurde in zwei Experimentserien empirisch getestet: Experimente Ia (N=24) und Ib (N=27) verwendeten eine globale Auflösungsaufgabe, bei der die Versuchspersonen ein pronominales Nebensatzgefüge lasen und den intendierten Referenten benannten. Es ergab sich, dass der IC-Erleichterungseffekt bei früher Signalisierung ein Refokussierungs-, ohne jedoch ein Integrations-Effekt ist. In den Experimenten IIa (N=25) und IIb (N=23) wurde zusätzlich die Dynamik der beteiligten Prozesse untersucht, indem mittels einer self-paced-reading-Aufgabe der Verarbeitungsaufwand im Satzverlauf kontinuierlich erhoben wurde. Erwartungsgemäß traten die hierarchie-niedrigen Refokussierungs-Prozesse früh auf, während sich die hierarchie-hohen Integrations-Prozesse allein satzfinal nachweisen ließen. In beiden Experimenten war das Auftreten von Refokussierungs-Prozessen jedoch an die Bedingung geknüpft, dass ein hinreichend starker Diskurskontext zur frühen Reanalyse zur Verfügung stand

Devitalization of Glioblastoma Cancer Cells by Non-invasive Physical Plasma: Modulation of Proliferative Signalling Cascades

Background/Aim: Glioblastoma (GBM) is the most common and most lethal type of cancer of the central nervous system in adults. Despite aggressive treatment, which is based on surgical resection, if possible, followed by radiation and chemotherapy, a high recurrence rate and therapy resistance is observed. Thus, additional innovative therapies are urgently needed to improve the poor median survival of only 15 months. Treatment of solid tumours with non-invasive physical plasma (NIPP) represents such a novel and innovative anticancer procedure. Materials and Methods: In this study, we investigated the effect of NIPP, an ionized argon gas, on the in vitro growth of human GBM cell lines, LN-18 and U-87 MG. Proliferation was measured by live cell count. Subsequently, proliferative factors were analysed at the level of nucleic acids (polymerase chain reaction) and proteins (western blotting). Results: For both GBM lines, a treatment time-dependent decrease in growth was observed compared to controls. Additionally, NIPP treatment resulted in reduced rates of AKT serine/threonine kinase 1 (AKT1) and extracellular-regulated kinase 1/2 ERK1/2 expression, whereas expression of p21, proliferating cell nuclear antigen, and heat-shock proteins 90α and 90β was not affected. In both cell lines, a strong increase in expression of tumour-suppressive microRNA-1 (miR-1) was detected after exposure to NIPP. Conclusion: Our results demonstrated that NIPP is able to efficiently attenuate growth of GBM cells and suggest AKT1, ERK1/2 and miR-1 to be pivotal factors of NIPP-modulated cellular signalling. Translated into the clinical setting, NIPP may represent a promising option for the treatment of GBM

Orthographic consistency influences morphological processing in reading aloud: Evidence from a cross‐linguistic study

International audienc

Eye Movements of Children and Adults Reading in Three Different Orthographies

In this study, we investigated developmental aspects of eye movements during reading of three languages (English, German and Finnish) that vary widely in their orthographic complexity and predictability . Grapheme-phoneme correspondence rules are rather complex in English and German but relatively simple in Finnish. Despite their differences in complexity, the rules in German and Finnish are highly predictable, whereas English has many exceptions. Comparing eye movement development in these three languages, thus, allows us to investigate whether orthographic complexity and predictability have separate effects on eye movement development. Three groups of children, matched on years of reading instruction, along with a group of proficient adult readers in each language were tested. All participants read stimulus materials that were carefully translated and back-translated across all three languages. The length and frequency of 48 target words were manipulated experimentally within the stimulus set. For children, word length effects were stronger in Finnish and German than in English. In addition, in English effects of word frequency were weaker and only present for short words . Generally, English children showed a qualitatively different reading pattern, while German and Finnish children’s reading behavior was rather similar. These results indicate that the predictability of an orthographic system is more important than its complexity for children’s reading development . Adults’ reading behavior, in contrast, was remarkably similar across languages. Our results, thus, demonstrate that eye movements are sensitive to language-specific features in children’s reading, but become more homogenous as reading skill matures

Immunophenotyping of Circulating and Intratumoral Myeloid and T Cells in Glioblastoma Patients

Glioblastoma is the most common and lethal primary brain malignancy that almost inevitably recurs as therapy-refractory cancer. While the success of immune checkpoint blockade (ICB) revealed the immense potential of immune-targeted therapies in several types of cancers outside the central nervous system, it failed to show objective responses in glioblastoma patients as of now. The ability of glioblastoma cells to drive multiple modes of T cell dysfunction while exhibiting low-quality neoepitopes, low-mutational load, and poor antigen priming limits anti-tumor immunity and efficacy of antigen-unspecific immunotherapies such as ICB. An in-depth understanding of the GBM immune landscape is essential to delineate and reprogram such immunosuppressive circuits during disease progression. In this view, the present study aimed to characterize the peripheral and intratumoral immune compartments of 35 glioblastoma patients compared to age- and sex-matched healthy control probands, particularly focusing on exhaustion signatures on myeloid and T cell subsets. Compared to healthy control participants, different immune signatures were already found in the peripheral circulation, partially related to the steroid medication the patients received. Intratumoral CD4+ and CD8+ TEM cells (CD62Llow/CD45ROhigh) revealed a high expression of PD1, which was also increased on intratumoral, pro-tumorigenic macrophages/microglia. Histopathological analysis further identified high PSGL-1 expression levels of the latter, which has recently been linked to increased metastasis in melanoma and colon cancer via P-selectin-mediated platelet activation. Overall, the present study comprises immunophenotyping of a patient cohort to give implications for eligible immunotherapeutic targets in neurooncology in the future

Regulatory interactions between IRG resistance GTPases in the cellular response to Toxoplasma gondii

Members of the immunity-related GTPase (IRG) family are interferon-inducible resistance factors against a broad spectrum of intracellular pathogens including Toxoplasma gondii. The molecular mechanisms governing the function and regulation of the IRG resistance system are largely unknown. We find that IRG proteins function in a system of direct, nucleotide-dependent regulatory interactions between family members. After interferon induction but before infection, the three members of the GMS subfamily of IRG proteins, Irgm1, Irgm2 and Irgm3, which possess an atypical nucleotide-binding site, regulate the intracellular positioning of the conventional GKS subfamily members, Irga6 and Irgb6. Following infection, the normal accumulation of Irga6 protein at the parasitophorous vacuole membrane (PVM) is nucleotide dependent and also depends on the presence of all three GMS proteins. We present evidence that an essential role of the GMS proteins in this response is control of the nucleotide-bound state of the GKS proteins, preventing their GTP-dependent activation before infection. Accumulation of IRG proteins at the PVM has previously been shown to be associated with a block in pathogen replication: our results relate for the first time the enzymatic properties of IRG proteins to their role in pathogen resistance

Uptake Mechanism of ApoE-Modified Nanoparticles on Brain Capillary Endothelial Cells as a Blood-Brain Barrier Model

Background: The blood-brain barrier (BBB) represents an insurmountable obstacle for most drugs thus obstructing an effective treatment of many brain diseases. One solution for overcoming this barrier is a transport by binding of these drugs to surface-modified nanoparticles. Especially apolipoprotein E (ApoE) appears to play a major role in the nanoparticle-mediated drug transport across the BBB. However, at present the underlying mechanism is incompletely understood. Methodology/Principal Findings: In this study, the uptake of the ApoE-modified nanoparticles into the brain capillary endothelial cells was investigated to differentiate between active and passive uptake mechanism by flow cytometry and confocal laser scanning microscopy. Furthermore, different in vitro co-incubation experiments were performed with competing ligands of the respective receptor. Conclusions/Significance: This study confirms an active endocytotic uptake mechanism and shows the involvement of low density lipoprotein receptor family members, notably the low density lipoprotein receptor related protein, on the uptake of the ApoE-modified nanoparticles into the brain capillary endothelial cells. This knowledge of the uptake mechanism of ApoE-modified nanoparticles enables future developments to rationally create very specific and effective carriers to overcome the blood-brain barrier

Toxin Mediated Diarrhea in the 21st Century: The Pathophysiology of Intestinal Ion Transport in the Course of ETEC, V. cholerae and Rotavirus Infection

An estimated 4 billion episodes of diarrhea occur each year. As a result, 2–3 million children and 0.5–1 million adults succumb to the consequences of this major healthcare concern. The majority of these deaths can be attributed to toxin mediated diarrhea by infectious agents, such as E. coli, V. cholerae or Rotavirus. Our understanding of the pathophysiological processes underlying these infectious diseases has notably improved over the last years. This review will focus on the cellular mechanism of action of the most common enterotoxins and the latest specific therapeutic approaches that have been developed to contain their lethal effects