Beeinflusst Stereotype Threat die Leseleistung von Jungen?

Ein durchgängiger Befund internationaler Schulleistungsvergleichsstudien bezieht sich auf die niedrigere Lesekompetenz von Jungen im Vergleich zu Mädchen (OECD, 2010). Ziel der vorliegenden Arbeit war, zu prüfen, welchen Einfluss negative Stereotype – im Sinne der Stereotype Threat-Theorie (Steele & Aronson, 1995) – auf die Leseleistung von Jungen haben. Basierend auf Befunden aus der Lese- und Stereotype Threat-Forschung wurde ein Mediator-Moderator-Modell des Stereotype Threat-Effekts (vgl. Schmader, Johns & Forbes, 2008) auf die Leseleistung von Jungen abgeleitet und überprüft. Um diese Fragestellungen zu beantworten, wurden zwei quasiexperimentelle Untersuchungen mit Schülern achter und neunter Klassen durchgeführt. An der ersten Untersuchung nahmen insgesamt 167 Schüler (n = 69 Jungen, n = 98 Mädchen) zweier Gymnasien in privater Trägerschaft teil. Um die Fragestellungen an einer weniger selektiven Stichprobe untersuchen zu können, erfolgte eine zweite Untersuchung mit Schülern (N = 441) öffentlicher Schulen und verschiedener Schulformen, wobei der Fokus ausschließlich auf den männlichen Schülern (n = 188 Jungen; n = 122 Gymnasiasten, n = 66 Realschüler plus) lag. Für beide Experimente kann zusammenfassend festgehalten werden, dass sich, entgegen der Erwartungen, kein leistungsmindernder Stereotype Threat-Effekt auf die Leseleistung von Jungen zeigte. Ferner konnten keine signifikante Mediatoren und Moderatoren eines leistungsmindernden Stereotype Threat-Effekts auf die Leseleistung von Jungen identifiziert werden. Ziel zukünftiger Forschung muss sein, den Einfluss negativer Stereotype auf die Leistungen männlicher Probanden im Sinne von Mitgliedern dominanter Gruppen zu untersuchen. Besonderes Augenmerk sollte auf die stereotypisierte Fähigkeitsdomäne gelegt werden. Weiterhin ist wichtig, der Frage nach zugrunde liegenden Prozessen und Voraussetzungen für das Erleben von Stereotype Threat nachzugehen. Studien weisen darauf hin, dass unterschiedlich stigmatisierte Gruppen unterschiedlich auf Stereotype Threat reagieren. Daher sollte der Fokus zukünftiger Forschung darauf liegen, die Prozesse und Voraussetzungen näher zu untersuchen, die für Mitglieder sonst positiv stereotypisierter Gruppen in solchen Situationen zum Tragen kommen.

Entrepreneurship influential factors in development of rural tourism as diversified rural activity in Republic of Macedonia

Rural tourism is relatively new product in the process of diversification of the rural economy in Republic of Macedonia. This study used desk research and life story interviews of rural tourism entrepreneurs as qualitative research method to identify prevalent success influential factors. Further quantitative analysis was applied in order to measure the strength of influence of identified success factors. The primary data for the quantitative research was gathered using telephone questionnaire composed of 37 questions with 5-points Likert scale. The data was analyzed using Partial Least Squares Structural Equation Modeling (PLS-SEM) by SmartPLS 3.1.6. Results indicated that human capital, social capital, entrepreneurial personality and external business environment are predominant influential success factors. However, human capital has non-significant direct effect on success (p 0.493) nonetheless the effect was indirect with high level of partial mediation through entrepreneurial personality as mediator (VAF 73%). Personality of the entrepreneur, social capital and business environment have direct positive affect on entrepreneurial success (p 0.001, 0.003 and 0.045 respectably). Personality also mediates the positive effect of social capital on entrepreneurial success (VAF 28%). Opposite to the theory the data showed no interaction between social and human capital on the entrepreneurial success. This research suggests that rural tourism accommodation entrepreneurs could be more successful if there is increased support in development of social capital in form of conservation of cultural heritage and natural attractions. Priority should be finding the form to encourage and support the establishment of formal and informal associations of entrepreneurs in order to improve the conditions for management and marketing of the sector. Special support of family businesses in the early stages of the operation would have a particularly positive impact on the success of rural tourism. Local infrastructure, access to financial instruments, destination marketing and entrepreneurial personality have positive effect on success.

Zelluläre und molekulare Mechanismen der angeborenen Immunität

Die myeloide Zelllinie MUTZ-3 konnte als geeignetes Modellsystem zur Charakterisierung der TREM-1-Signaltransduktion etabliert werden, da diese TREM-1 und dessen essentielles Adaptermoleküle DAP12 funktional exprimiert. Übereinstimmend mit bisherigen Daten wurden die Kinasen PI3K und p38-MAPK als wichtige Regulatoren in der Signalweiterleitung nach TREM-1-Aktivierung identifiziert, wobei sich einige Unterschiede in der exakten Signalhierarchie zwischen monozytären und granulozytären Zellen ergaben. So erfolgt die Aktivierung von PI3K und p38-MAPK in PMN unabhängig voneinander und in monozytären Zellen findet die Aktivierung von p38-MAPK vor der Akt-Phosphorylierung statt und ist für Letztere notwendig. Zudem ist die Ca2+-Mobilisierung in PMN nur von PI3K abhängig und in monozytären Zellen von PI3K und p38-MAPK. Bei der durch TLR- oder NLR-Koligation gesteigerten TREM-1-Aktivierung sind PI3K und p38-MAPK ebenfalls zentrale Regulatoren. Es ergaben sich ebenfalls Unterschiede in der exakten TREM-1-Signaltransduktion.rnrnEin Mausmodell für invasive Aspergillose (IA) wurde erfolgreich etabliert, wobei die wichtige Rolle der PMN bei der Abwehr von Pilzinfektionen durch deren Depletion mit unterschiedlichen Antikörpern belegt wurde. Für das Abtöten von A. fumigatus-Konidien sind oxidative und nicht-oxidative PMN-Effektormechanismen notwendig. Dabei konnte die essentielle Rolle der oxidativen PMN-Effektorfunktionen anhand NADPH-Oxidase-defizienter p47phox-/- und gp91phox-/- Mäuse für das Überleben von Pilzinfektionen gezeigt werden. Dagegen war die Infektion von Neutrophiler Elastase defizienter ELANE Mäuse nicht letal. Dies deutet darauf hin, dass diese als prototypische Serinprotease und wichtiger Bestandteil der NET-Formation nicht essentiell für das Überleben von IA ist oder durch andere, nicht-oxidative Effektormechanismen kompensiert werden kann. Keinen Einfluss auf die IA hatte die Depletion von Arginin mittels ADI-PEG, da weder das Überleben der Mäuse noch das Abtöten der Pilzkonidien beeinflusst wurde. Außerdem wurden keine Veränderung in der Einwanderung und Aktivierung von PMN nach Infektion quantifiziert. Dagegen induzierte die Defizienz in ADAMTS13 (ADAMTS13-/- Mäuse) eine verminderte Rekrutierung von PMN, einhergehend mit erhöhter Mortalität, vermindertem Abtöten von A. fumigatus-Konidien und erhöhter Schädigung der Lunge bei IA. Da in vitro keine generellen oder pilzspezifischen Defekte der PMN quantifiziert wurden, muss ADAMTS13 die Einwanderung der PMN beeinflussen. Normalerweise spaltet die Protease ADAMTS13 den von-Willebrand-Faktor (vWF), der die Quervernetzung und das Anhaften von Blutplättchen an beschädigte Gefäßwände steuert. Ob und wie ADAMTS13 oder der vWF die verminderte PMN-Einwanderung bei Pilzinfektionen verursacht, muss weiter untersucht werden.rnrnZusammenfassend verbessern die erhaltenen Daten für eine zellspezifische TREM-1-Signaltransduktion, ein von oxidativen und nicht-oxidativen PMN-Effektorfunktionen abhängiges sowie Arginin-unabhängiges Abtöten vom Pilz A. fumigatus als auch der Einfluss von ADAMTS13 und vWF bei der Rekrutierung von PMN nach A. fumigatus-Infektion unser Verständnis der angeborenen Immunität. Diese Erkenntnisse dienen der zukünftigen Entwicklung von Therapien zur Behandlung von schweren Entzündungsreaktionen wie Aspergillose und Sepsis.

Regulation des Proteins Alpha-Synuclein während der zellulären Alterung

α-Synuclein wird durch Mutationen sowie der Ausbildung von Proteinaggregaten namens Lewy-Körperchen mit der Entstehung der altersassoziierten Parkinson-Krankheit in Verbindung gebracht. Sowohl familiäre als auch sporadische Fälle sind durch erhöhte α-Synuclein-Spiegel gekennzeichnet. In familiären Fällen wurden Multiplikationen des α-Synuclein-Gens als Ursache für die erhöhte Expression aufgedeckt. In sporadischen Fällen stellt die Alterung den entscheidenden Risikofaktor für die Entstehung der Krankheit dar. Daher wurde in der vorliegenden Arbeit die Regulation von α-Synuclein während der zellulären Alterung in humanen Fibroblasten untersucht. In seneszenten Zellen konnte ein Anstieg der α-Synuclein-Expression nachgewiesen werden, der jedoch die Löslichkeit des Proteins nicht veränderte. Damit scheint die zelluläre Alterung per se nicht für die Aggregation des Proteins, wie sie in Form von Lewy-Körperchen bei z. B. Patienten der Parkinson-Krankheit beobachtet wird, verantwortlich zu sein. Möglicherweise ist die Hochregulation von α-Synuclein eine Folge der Akkumulation von DNA-Schäden in den seneszenten Zellen. Diese Korrelation konnte in jungen Zellen nach dem Einsatz verschiedener DNA-schädigender Agenzien bestätigt werden. Die Untersuchung des Regulationsmechanismus ergab, dass die erhöhte Expression von α-Synuclein in Folge von DNA-Schäden über den ERK1/2-MAPK-Signalweg vermittelt wird. In seneszenten Zellen konnte ebenfalls ein Einfluss dieses Signalweges auf die Expression von α-Synuclein beobachtet werden, allerdings scheint dieser nicht alleinig für die Hochregulation verantwortlich zu sein. Des Weiteren ergab die Betrachtung des γH2A.X-Spiegels nach Induktion von DNA-Schäden, dass α-Synuclein möglicherweise eine protektive Funktion besitzt, da dessen Überexpression zu einer verringerten und die Herunterregulation zu einer vermehrten DNA-Schädigung führte. Die Analyse der subzellulären Lokalisation von α-Synuclein ergab außerdem, dass es in jungen Zellen nach der Induktion von DNA-Schäden zu einer Translokation des Proteins in den Zellkern kommt. Diese Translokation war in seneszenten Zellen verringert. Dies lässt vermuten, dass α-Synuclein in jungen Zellen nach DNA-Schädigung durch den ERK1/2-MAPK-Signalweg hochreguliert wird und durch die Translokation in den Zellkern möglicherweise die Transkription von protektiven Genen beeinflusst oder an DNA-Reparatur-Prozessen beteiligt ist. In seneszenten Zellen ist das Protein zwar deutlich stärker exprimiert, der Transport in den Zellkern jedoch verringert, wodurch die protektive Wirkung im Zellkern herabgesetzt wäre.

Il child language brokering a Ravenna e provincia: la parola agli studenti e ai professori

The main aim of this study is to provide a description of the phenomenon defined as Child Language Brokering (CLB), a common practice among language minority communities but which has received less attention in the academic literature. As the children of immigrants often learn the host language much more quickly than their parents, they contribute to family life by acting as language and cultural mediators between a family members and different language speakers. Many immigrant families prefer a language broker from within their own family to an external mediator or interpreter, even though there is a well-found resistance to the use of these young interpreters by professionals. In this study I report some findings from surveys of teachers in schools in Ravenna where there has been some use of students as CLBs and of students who have acted or are still acting as mediators for their families in different contexts, not only while at school. This dissertation is divided into five chapters. Chapter one aims at providing an overview of recent migration to Italy and of the differences between first-generation immigrants and second-generation immigrants. The chapter also discusses the available professional interpreting facilities provided by the municipality of Ravenna. Chapter two presents an overview of the literature on child language brokering. Chapter three provides a description of the methodology used in order to analyze the data collected. Chapter four contains a detailed analysis of the questionnaires administered to the students and the interviews submitted to the teachers in four schools in Ravenna. Chapter five focuses on the studies carried out by the researchers of the Thomas Coram Research Unit and University College London and draws a general comparison between their findings from on-line surveys of teachers in schools and my own findings on teachers’ points of view. The results of this study demonstrate that CLB is a common practice among immigrant children living in Ravenna and, although almost all students reported positive appreciation, further work is still needed to assess the impact of this phenomenon.

Tumor necrosis factor sensitizes primary murine hepatocytes to Fas/CD95-induced apoptosis in a Bim- and Bid-dependent manner

Fas/CD95 is a critical mediator of cell death in many chronic and acute liver diseases and induces apoptosis in primary hepatocytes in vitro. In contrast, the proinflammatory cytokine tumor necrosis factor α (TNFα) fails to provoke cell death in isolated hepatocytes but has been implicated in hepatocyte apoptosis during liver diseases associated with chronic inflammation. Here we report that TNFα sensitizes primary murine hepatocytes cultured on collagen to Fas ligand (FasL)-induced apoptosis. This synergism is time-dependent and is specifically mediated by TNFα. Fas itself is essential for the sensitization, but neither Fas up-regulation nor endogenous FasL is responsible for this effect. Although FasL is shown to induce Bid-independent apoptosis in hepatocytes cultured on collagen, the sensitizing effect of TNFα is clearly dependent on Bid. Moreover, both c-Jun N-terminal kinase activation and Bim, another B cell lymphoma 2 homology domain 3 (BH3)-only protein, are crucial mediators of TNFα-induced apoptosis sensitization. Bim and Bid activate the mitochondrial amplification loop and induce cytochrome c release, a hallmark of type II apoptosis. The mechanism of TNFα-induced sensitization is supported by a mathematical model that correctly reproduces the biological findings. Finally, our results are physiologically relevant because TNFα also induces sensitivity to agonistic anti-Fas-induced liver damage. CONCLUSION: Our data suggest that TNFα can cooperate with FasL to induce hepatocyte apoptosis by activating the BH3-only proteins Bim and Bid.

BTLA mediates inhibition of human tumor-specific CD8+ T cells that can be partially reversed by vaccination

The function of antigen-specific CD8+ T cells, which may protect against both infectious and malignant diseases, can be impaired by ligation of their inhibitory receptors, which include CTL-associated protein 4 (CTLA-4) and programmed cell death 1 (PD-1). Recently, B and T lymphocyte attenuator (BTLA) was identified as a novel inhibitory receptor with structural and functional similarities to CTLA-4 and PD-1. BTLA triggering leads to decreased antimicrobial and autoimmune T cell responses in mice, but its functions in humans are largely unknown. Here we have demonstrated that as human viral antigen-specific CD8+ T cells differentiated from naive to effector cells, their surface expression of BTLA was gradually downregulated. In marked contrast, human melanoma tumor antigen-specific effector CD8+ T cells persistently expressed high levels of BTLA in vivo and remained susceptible to functional inhibition by its ligand herpes virus entry mediator (HVEM). Such persistence of BTLA expression was also found in tumor antigen-specific CD8+ T cells from melanoma patients with spontaneous antitumor immune responses and after conventional peptide vaccination. Remarkably, addition of CpG oligodeoxynucleotides to the vaccine formulation led to progressive downregulation of BTLA in vivo and consequent resistance to BTLA-HVEM-mediated inhibition. Thus, BTLA activation inhibits the function of human CD8+ cancer-specific T cells, and appropriate immunotherapy may partially overcome this inhibition.

Icatibant, a new bradykinin-receptor antagonist, in hereditary angioedema

Hereditary angioedema is characterized by recurrent attacks of angioedema of the skin, larynx, and gastrointestinal tract. Bradykinin is the key mediator of symptoms. Icatibant is a selective bradykinin B2 receptor antagonist.

DARPins against a functional IgE epitope

The monoclonal anti-IgE antibody omalizumab (Xolair is mostly used for the treatment of severe allergic asthma. However, the requirement of high doses and suboptimal cost-effectiveness limits the use of the treatment. Here we propose to use a new drug format based on non-immunoglobulin structures, potentially offering increased clinical efficacy while being more cost-effective. For this purpose, DARPins (designed ankyrin repeat proteins) against the constant heavy chain region of IgE have been isolated. DARPins were binding to IgE with high specificity and affinities in the low nanomolar range. Selected DARPins antagonized the interaction between IgE and its high-affinity receptor in inhibition assays. Furthermore, anti-IgE DARPins were shown to inhibit proinflammatory mediator release from rat basophilic leukemia cells expressing human high-affinity IgE receptors with higher efficacy than the monoclonal anti-IgE antibody omalizumab. DARPins may thus represent promising future drug candidates for the treatment of allergy.

Monocyte differentiation toward regulatory dendritic cells is not affected by respiratory syncytial virus-induced inflammatory mediators

Airway epithelial cells were shown to drive the differentiation of monocytes into dendritic cells (DCs) with a suppressive phenotype. In this study, we investigated the impact of virus-induced inflammatory mediator production on the development of DCs. Monocyte differentiation into functional DCs, as reflected by the expression of CD11c, CD123, BDCA-4, and DC-SIGN and the capacity to activate T cells, was similar for respiratory syncytial virus (RSV)-infected and mock-infected BEAS-2B and A549 cells. RSV-conditioned culture media resulted in a partially mature DC phenotype, but failed to up-regulate CD80, CD83, CD86, and CCR7, and failed to release proinflammatory mediators upon Toll-like receptor (TLR) triggering. Nevertheless, these DCs were able to maintain an antiviral response by the release of Type I IFN. Collectively, these data indicate that the airway epithelium maintains an important suppressive DC phenotype under the inflammatory conditions induced by infection with RSV.

The targeting of plasmalemmal ceramide to mitochondria during apoptosis

Ceramide is a key lipid mediator of cellular processes such as differentiation, proliferation, growth arrest and apoptosis. During apoptosis, ceramide is produced within the plasma membrane. Although recent data suggest that the generation of intracellular ceramide increases mitochondrial permeability, the source of mitochondrial ceramide remains unknown. Here, we determine whether a stress-mediated plasmalemmal pool of ceramide might become available to the mitochondria of apoptotic cells. We have previously established annexin A1--a member of a family of Ca(2+) and membrane-binding proteins--to be a marker of ceramide platforms. Using fluorescently tagged annexin A1, we show that, upon its generation within the plasma membrane, ceramide self-associates into platforms that subsequently invaginate and fuse with mitochondria. An accumulation of ceramide within the mitochondria of apoptotic cells was also confirmed using a ceramide-specific antibody. Electron microscopic tomography confirmed that upon the formation of ceramide platforms, the invaginated regions of the plasma membrane extend deep into the cytoplasm forming direct physical contacts with mitochondrial outer membranes. Ceramide might thus be directly transferred from the plasma membrane to the mitochondrial outer membrane. It is conceivable that this "kiss-of-death" increases the permeability of the mitochondrial outer membrane thereby triggering apoptosis.

Loss of sphingosine kinase-1 in carcinoma cells increases formation of reactive oxygen species and sensitivity to doxorubicin-induced DNA damage

Sphingosine kinases (SK) catalyse the formation of sphingosine 1-phosphate, which is a key lipid mediator regulating cell responses such as proliferation, survival and migration. Here we have investigated the effect of targeted inhibition of SK-1 on cell damage and elucidated the mechanisms involved.

Glycomic analysis of human mast cells, eosinophils and basophils

In allergic diseases such as asthma, eosinophils, basophils and mast cells, through release of preformed and newly generated mediators, granule proteins and cytokines, are recognized as key effector cells. While their surface protein phenotypes, mediator release profiles, ontogeny, cell trafficking and genomes have been generally explored and compared, there has yet to be any thorough analysis and comparison of their glycomes. Such studies are critical to understand the contribution of carbohydrates to the induction and regulation of allergic inflammatory responses and are now possible using improved technologies for detecting and characterizing cell-derived glycans. We thus report here the application of high-sensitivity mass spectrometric-based glycomics methodologies to the analysis of N-linked glycans derived from isolated populations of human mast cells, eosinophils and basophils. The samples were subjected to matrix-assisted laser desorption ionization (MALDI) time-of-flight (TOF) screening analyses and MALDI-TOF/TOF sequencing studies. Results reveal substantive quantities of terminal N-acetylglucosamine containing structures in both the eosinophil and the basophil samples, whereas mast cells display greater relative quantities of sialylated terminal epitopes. For the first time, we characterize the cell surface glycan structures of principal allergic effector cells, which by interaction with glycan-binding proteins (e.g. lectins) have the possibility to dictate cellular functions, and might thus have important implications for the pathogenesis of inflammatory and allergic diseases.

Lethal mitochondrial cardiomyopathy in a hypomorphic Med30 mouse mutant is ameliorated by ketogenic diet

Deficiencies of subunits of the transcriptional regulatory complex Mediator generally result in embryonic lethality, precluding study of its physiological function. Here we describe a missense mutation in Med30 causing progressive cardiomyopathy in homozygous mice that, although viable during lactation, show precipitous lethality 2-3 wk after weaning. Expression profiling reveals pleiotropic changes in transcription of cardiac genes required for oxidative phosphorylation and mitochondrial integrity. Weaning mice to a ketogenic diet extends viability to 8.5 wk. Thus, we establish a mechanistic connection between Mediator and induction of a metabolic program for oxidative phosphorylation and fatty acid oxidation, in which lethal cardiomyopathy is mitigated by dietary intervention.

Inhibition of ongoing allergic reactions using a novel anti-IgE DARPin-Fc fusion protein

Aggregation of the high-affinity IgE receptor (FcεRI) with the low-affinity IgG receptor (FcγRIIb) on basophils or mast cells has been shown to inhibit allergen-induced cell degranulation. Molecules cross-linking these two receptors might therefore be of interest for the treatment of allergic disorders. Here, we demonstrate the generation of a novel bispecific fusion protein efficiently aggregating FcεRI-bound IgE with FcγRIIb on the surface of basophils to prevent pro-inflammatory mediator release.