511 research outputs found
From grammar to theology: history of a word. Διαστολή and related terms in Origen and in the origenian tradition, in: Origeniana Decima. Atti del Colloquium Origenianum Decimum su “Origene e la tradizione alessandrina” [Cracovia, 31 agosto – 4 settembre 2009], a c. di H. PIETRAS – A. DZIADOWIEC, [in corso di stampa presso Peeters (Bibliotheca Ephemeridum Theologicarum Lovaniensium), Leuven]
No full textThrough a bird’s-eye view of the use of the terms διαστολή/ἀντιδιαστολή, it seems quite clear that the passage of this word from the semantic domain of grammar and philology to that one of theological debates – as shown by the later texts quoted – can be considered beyond any doubt as another step of Origen’s Wirkungsgeschichte
Origenes pro domo sua: Self-Quotations and the (Re-) Construction of a literary œuvre
No full textThe aim of the article is not to reopen the dossier of the self-quotations in order to reexamine their exploitation for a chronology of Origen’s works, as established by Nautin and others, although it is not possible to ignore this problem altogether. I am indeed interested in exploring self-quotations as useful clues for a better understanding of what we may call Origen’s ‘literary pragmatics’ as far as the author himself is concerned
On the Council of Nicea (325) in the light of the monograph by Henryk Pietras SJ
No full textThe Council convened by emperor Constantine the Great to Nicea in the year 325 still arouses keen interest of researchers around the world. Against the background of international scholarship, the achievements of Polish academics look quite modest. That is why one should especially appreciate the publication of a book (written in Polish) on the subject by Henryk Pietras, an acclaimed Polish patrologist. The monograph is noteworthy for a number of reasons and compels the reader to a thorough reflection on a cornucopia of facts that have been already discussed by numerous academics and subject to manifold interpretations. Its special merit lies first and foremost in an erudite analysis of sources conducted by the Author, which is competent enough to exhort all the interested to (at least) re-think their views. It is necessary to admit that the Academic is right, when he argues that the Council (firstly convened to Ancyra, and subsequently to Nicea) was not organized for the reason of discussing the Arian controversy. In reality, it seems that the primary reason for the meeting was the Donatist schism, which the Patrologist underestimated, and additionally the problem of reaching an agreement on a date of the Passover celebration. Certainly, the Council was not of an anti-Arian nature, but Arius was condemned by the ecclesiastic meeting as the one who rejected a laboriously reached compromise as for the form of the credo and renounced the term homoousios
Interaction and regulation of asthma susceptibility genes
No full textAsthma is a disorder characterized by symptoms such as wheezing, shortness of breath, chest tightness or coughing. It is a chronic inflammation in the airways and the inflammation is usually accompanied by limitations in airflow as a result of hyper-secretion of mucus and broncho-constriction. Asthma commonly coincides with other allergic diseases such as allergic sensitization and rhinoconjunctivitis. The prevalence of asthma and allergy in children is highest in affluent countries with up to 20% in English speaking countries. Asthma and allergic disease are complex disorders and have long been known to be influenced by both heritable components and environmental factors.The overall aim with this thesis was to investigate asthma susceptibility genes and their genetic role, biological dependency, as well as how they interact in a context-dependent manner, either with other genes (I) or with environmental factors (II). We studied the functional difference between splice variants of a previously identified asthma susceptibility gene showing unique expression patterns in asthmatic patients (III). We also aimed to define global gene expression patterns in asthmatic children that could reveal novel insight about characteristics of severe therapy-resistant asthma in children (IV).In study I, we examined the biologically linked asthma susceptibility gene Tenascin C (TNC) and its genetic role in asthma and allergy. We also investigated the biological and genetic interactions between TNC and the previously genetically identified asthma susceptibility gene Neuropeptide S receptor 1 (NPSR1).In study II, we investigated the interactive effects of NPSR1 and environmental exposures related to farming lifestyle, as well as the effect of lipopolysaccharide (LPS), a proxy for farm animal exposure, on NPSR1 expression. We provide data showing that TNC has an independent genetic role in certain allergic diseases. We show biological interplay by a dose-dependent upregulation of TNC expression upon NPS-NPSR1 activation, and we conclude that interaction occurs between TNC and NPSR1altering the outcome of asthma and allergy. Genetic variations in NPSR1 are not only dependent on other genes, but can also modify the effect of the environment, on the development of allergic diseases. Farm animal contact and farm milk consumption, introduced early in a child’s life, has been proven to show protective effects against development of allergic diseases.In study II, we demonstrate that the protective effect of farm animal contact can be further modified depending on genetic variations in NPSR1, especially if the contact is initiated later in life. We also identified increased NPSR1 expression upon LPS stimulation of human monocytes. From these two studies we can confirm that interactive effects, both biological and genetic, are important in the development of asthma and allergy. We could also see that the genetic dependency is most likely to occur when the main effect of the individual genes, or environmental factors, investigated are not that dominant.In study III, we investigated the function of NPSR1 in more detail. The NPSR1 gene encodes two functional receptor variants (A and B) with distinct intracellular C-termini. Previous studies have illustrated different expression pattern, especially in asthmatic airways, between the two receptor variants. We could in study III demonstrate that, upon activation, both receptor variants A and B signals through the same pathways and induces expression of in principal identical set of genes. However, with few exceptions, variant A constantly induced stronger signaling effects than variant B. The effect was seen on both second messenger level and on down-stream gene expression. These findings suggest an isoform specific link to NPSR1s role in allergic airways. Among children with asthma around 5% suffer from chronic symptoms and/or severe exacerbation despite extensive treatment. The causes of this severe, therapy resistant asthma in childhood are poorly understood.In study IV we aimed to investigate global differences in gene expression in white blood cells from patients with severe, therapy-resistant asthma (SA, n=20), patients with controlled but persistent asthma (CA, n=20) and a group of healthy controls (Ctrl, n=19). We identified 1378 genes to be significantly differentially expressed between any of the contrasts (CA-Ctrl, SA-CA, SA-Ctrl) demonstrating that there are differences in gene expression between groups of asthma. Functional annotation and enrichment analysis identified three significantly differentially expressed pathways; bitter taste transduction, (upregulated mostly in SA), natural killer cell mediated cytotoxicity (upregulated in CA) and N-glycan biosynthesis (downregulated in SA). The bitter taste receptor family (TAS2Rs) has recently been shown to play a protective role in asthmatic airways e.g. by dilation of airways upon stimulation with bitter substances. Our finding is the first to propose a role for TAS2Rs in asthma outside the airway system.In conclusion our data indicates a separation in gene expression patterns between children with severe, therapy resistant asthma and controlled asthma, and suggests pathways revealing novel insight about the characteristics of severe therapy-resistant asthma. From the finding in this thesis we can conclude and confirm that there is always a complex interplay between several genes and environmental factors altering the outcome of allergic disease. It is important to investigate these genes in more detail to unravel the functional mode of action. We can also see that by investigating clear defined subgroups of asthma it might be possible to identify new therapeutic targets for asthma.List of scientific papersI. Christina Orsmark Pietras, Erik Melén, Johanna Vendelin, Sara Bruce, Annika Laitinen, Lauri A. Laitinen, Roger Launer, Josef Riedler, Erika von Mutius, Gert Doekes, Magnus Wickman, Marianne van Hage, Göran Pershagen, Annika Scheynius, Fredrik Nyberg, Juha Kere and the PARSIFAL Genetics Study Group. Biological and genetic interaction between Tenascin C and Neuropeptide S receptor 1 in allergic diseases. Human Molecular Genetics. 2008; 17: 1673-1682. https://doi.org/10.1093/hmg/ddn058 II. Sara Bruce, Fredrik Nyberg, Erik Melén, Anna James, Ville Pulkkinen, Christina Orsmark Pietras, Anna Bergström, Barbro Dahlén, Magnus Wickman, Erika von Mutius, Gert Doekes, Roger Launer, Josef Riedler, Waltraud Eder, Marianne van Hage, Göran Pershagen, Annika Scheynius, Juha Kere. The protective effect of farm animal exposure on childhood allergy is modified by NPSR1 polymorphisms. Journal of Medical Genetics. 2009; 46: 159-167. https://doi.org/10.1136/jmg.2007.055137 III. Christina Orsmark Pietras, Johanna Vendelin, Francesca Anedda, Sara Bruce, Mikael Adner, Lilli Sundman, Ville Pulkkinen, Harri Alenius, Mauro D’Amato, Cilla Söderhäll, Juha Kere. The asthma candidate gene NPSR1 mediates isoform specific downstream signaling. [Submitted]IV. Christina Orsmark Pietras, Jon Konradsen, Björn Nordlund, Cilla Söderhäll, Christophe Pedroletti, Gunilla Hedlin, Juha Kere, Erik Melén. Genome wide transcriptome analysis suggests novel mechanisms in severe childhood asthma. [Manuscript]</p
The asthma candidate gene <it>NPSR1 </it>mediates isoform specific downstream signalling
No full textAbstract Background Neuropeptide S Receptor 1 (NPSR1, GPRA, GPR154) was first identified as an asthma candidate gene through positional cloning and has since been replicated as an asthma and allergy susceptibility gene in several independent association studies. In humans, NPSR1 encodes two G protein-coupled receptor variants, NPSR1-A and NPSR1-B, with unique intracellular C-termini. Both isoforms show distinct expression pattern in asthmatic airways. Although NPSR1-A has been extensively studied, functional differences and properties of NPSR1-B have not yet been clearly examined. Our objective was to investigate downstream signalling properties of NPSR1-B and functional differences between NPSR1-A and NPSR1-B. Methods HEK-293 cells transiently overexpressing NPSR1-A or NPSR1-B were stimulated with the ligand neuropeptide S (NPS) and downstream signalling effects were monitored by genome-scale affymetrix expression-arrays. The results were verified by NPS concentration-response and time series analysis using qRT-PCR, cAMP and Ca2+ assays, and cAMP/PKA, MAPK/JNK and MAPK/ERK pathway specific reporter assays. Results NPSR1-B signalled through the same pathways and regulated the same genes as NPSR1-A, but NPSR1-B yielded lower induction on effector genes than NPSR1-A, with one notable exception, CD69, a marker of regulatory T cells. Conclusions We conclude that NPSR1-B is regulating essentially identical set of genes as NPSR1-A, with few, but possibly important exceptions, and that NPSR1-A induces stronger signalling effects than NPSR1-B. Our findings suggest an isoform-specific link to pathogenetic processes in asthma and allergy.</p
DNA vaccines to target the cancer testis antigen PASD1 in human multiple myeloma
No full textWe previously described PASD1 as a new cancer testis antigen in multiple myeloma (MM) that is retained post-therapy, suggesting the use of vaccination strategies to induce anti-PASD1 immunity in a setting of minimal residual disease. We have focused on DNA fusion gene vaccines, coupling fragment C domain (DOM) of tetanus toxin with PASD1 sequence, and examined efficacy in Human Leukocyte Antigen (HLA)-A2 (HHD) transgenic mice using a human MM cell line expressing PASD1 protein and chimeric HLA-A2 class I molecules as target. DNA vaccines encoded two HLA-A2-restricted epitopes (p.DOM-PASD1(1), p.DOM-PASD1(2)) and full-length PASD1 (p.DOM-PASD1FL). p.DOM-PASD1(1) proved superior to p.DOM-PASD1(2) in generating T-cell responses in HHD mice, able to lyse the chimeric murine RMA-HHD cells. Boosting by electroporation significantly enhanced p.DOM-PASD1(1). Only p.DOM-PASD1(1) induced cytotoxic T-lymphocytes (CTLs) were able to lyse human MM target cells expressing endogenous antigen. The p.DOM-PASD1FL vaccine predominantly induced strong PASD1(1) over PASD1(2) T-cell immune responses, indicative of immunodominance. Importantly, p.DOM-PASD1FL generated immune-mediating killing of native chimeric MM cells, in the absence of exogenous added peptide, implicating PASD1(1) specific CTLs. These data demonstrate that PASD1-derived epitopes are both efficiently and selectively processed and presented by native human MM cells. Notably, they permit the use of PASD1-encoding DNA vaccine therapy in a clinical setting
Co to znaczy być transcendentalnym idealistą i empirycznym realistą jednocześnie? O statusie rzeczy w filozofii transcendentalnej.
No full textThe aim of the article is to present an interpretation of the Kantian concept of transcendental idealism, which would make it possible to understand the status of things from the perspective of transcendental philosophy. The main claim of the article is that Kant’s standpoint can be situated beyond metaphysical realism and idealism, or, to use contemporary terms, beyond representationalism and constructivism. The standpoint in question can thus be regarded as an inspiration to reject the Cartesian dualism of substance and to propose a new philosophical perspective. In addition, the author claims that the understanding of transcendental philosophy presented in the article has provided a basis for the new, pluralist and relationalist ontology advanced by Nicolai Hartmann. She also suggests considering this ontology as another, after neo-Kantianism, stage in the development of German transcendental philosophy
Emil Lask: między neokantyzmem a postneokantyzmem
No full textIn this paper the author shows that Emil Lask’s philosophy starts with considering of typical Neo-Kantian’s questions but at the same time it grounds a new philosophical perspective – Post-Neo-Kantianism. The origin of Lask’s research is Heinrich Rickert’s theory of judgment, however Lask finds many new solutions and initiates new ideas adopted from him by Martin Heidegger. The article discuss an innovative elements of Lask’s thought like: problem of the material side of cognition, logic of object, logos-immanency of object, doctrine of the material determination of form, ontological theory of truth, problem of the individual subject. Although Lask does not create ontology, he makes transcendental philosophy to ask ontological questions. When we study his considerations it starts to be obvious that theory of cognition is not possible without ontology
W stronę ontologii. Nicolaia Hartmanna i Martina Heideggera postneokantowskie projekty filozofii
No full textThe subject of the book is two twentieth-century ontological projects: the critical ontology of Nicolai Hartmann and the fundamental ontology of Martin Heidegger. The author presents their works as well in a historical as a systematical perspective. The book focuses on those contexts of their thoughts, which have been often overlooked. Hartmann and Heidegger’s ontology is presented first in their relation to Kant, secondly in reference to neo-Kantianism, and thirdly in relation to each other. One of the main thesis of the book is that the most important difference between Hartmann and Heidegger’s interpretation of Kant, and - in consequence - also between their own projects of a new ontology, results from the ambiguity of Kant’s notion of things in themselves, which they interpret and use in a different way
Three views of the ‘musical work’. A study of conceptualisations in philosophical, bibliographical and editorial contexts within the domain of Music.
No full textThe author examines a choice of the conceptualisations of the ‘musical work’ within the domain of music in the context of bibliographical control and information retrieval. The study uses the principles of domain analysis proposed by Hjorland (Hjorland 2002) as a framework. The scope is wide and does not claim to be comprehensive. The philosophical and performance related conceptualisations of the musical work are examined with the method of discourse analysis of major writings on the topic. Each analysis is followed by an assessment of its relevance in the context of information organisation and user’s tasks. The phenomenological approach to the mode of being of musical work is examined with its particular applicability to modelling of the bibliographical entities in the domain of music. This is followed by further exploration of the bibliographical control of music and recent developments in FRBR/FRAD framework. The activity of editing music is presented in the context of its relevance to the practice of cataloguing music resources. In the conclusion the author points to the similarities of the activities of editors and information professionals in the context of critically informed choices they need to make when preparing either the text for the purpose of study or performance, or the catalogue record for the purpose of information retrieval. The shift in information organisation towards linked resources and the entities formulated as points of reference (including the main subject of this study – the ‘work’) beyond the library systems into the related resources on the world wide web is highlighted and the possibilities for further research in the context of the ‘work’ are suggested
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