Membrane proteomics characterization of brush border membrane proteins of mice intestinal mucosa : case study: cholesterol absorption

The epithelial absorbing cells of the small intestinal villi, the enterocytes, are the main protagonists for the transport of nutrients from the intestinal lumen to the interstitial fluids. The oriented flow of nutrients is carried out by different and complementary transport systems present in the apical and the basolateral domains of the enterocyte’s plasma membrane. One of the distinctive characteristics of those intestinal cells is the presence of numerous structurally distinct protrusions (referred as microvilli) on the apical surface of the plasma membrane. They confer the brush-like appearance of the microvillus border (commonly referred to as the "brush border") typically observed in the light microscope. Over the years, there has been considerable interest to study the molecular mechanisms driving the transport of molecules across the intestinal brush border membrane (BBM). Defects have been described to cause a variety of pathological conditions, such as disorders in the metabolism of saccharides (glucose and galactose malabsorption, lactose intolerance), amino acids (Hartnup disease, aminoacidurias), ions (sodium and potassium in the case of familiar diarrhea), metals (zinc in acrodermatitis enteropathica) and cholesterol lipids (cardiovascular diseases). In particular, the essential role of the BBM in regulating the delicate balance between cholesterol influx and efflux from the lumen to the enterocyte has been recently highlighted through the genetic analysis of individuals suffering of cholesterol disorders as well as in several clinical studies involving the use of dietary plant sterols (phytostrerols) or specific protein inhibitors blocking essential components of the cholesterol absorption/resorption pathway. ...Die absorbierenden Epithelzellen der Dünndarmzotten, die Enterozyten, spielen beim Transport der Nährstoffe vom intestinalen Lumen zu den interstitiellen Flüssigkeiten eine zentrale Rolle. Der gerichtete Fluss von Nährstoffen wird durch verschiedene komplementäre Transportsysteme gewährleistet, welche in den apikalen und basolateralen Domänen der Plasmamembrane der Enterozyten angesiedelt sind. Eine der besonderen Eigenschaften dieser Zellen ist das Vorkommen von zahlreichen Ausbuchtungen mit charakteristischer Struktur, sogenannten Mikrovilli, auf der apikalen Oberfläche der Plasmamembran. Diese verleihen dem Mikrovillusrand (auch als "Bürstensaum" bezeichnet) das bürstenartige Aussehen, das im Lichtmikroskop typischerweise sichtbar ist. Es besteht seit Jahren ein starkes Interesse an der Erforschung der molekularen Mechanismen, die für den Transport der Moleküle durch die intestinale Bürstensaum-Membran verantwortlich sind. Defekte in diesen Transportmechanismen können eine Vielzahl von pathologischen Problemen auslösen, wie zum Beispiel Störungen im Metabolismus von Sacchariden (Glukose- und Galaktose-Fehlabsorption, Lactoseunverträglichkeit), von Aminosäuren (Hartnup Krankheit, Aminoazidurie), von Ionen (Natrium und Kalium bei Durchfall), von Metallen (Zink bei acrodermatitis enteropathica) und von Cholesterinlipiden (Herzgefäßkrankheiten). Insbesondere wurde vor Kurzem die wesentliche Rolle der Bürstensaum-Membran bei der Regulierung des empfindlichen Gleichgewichts zwischen Cholesterinaufnahme und -abgabe zwischen Lumen und Enterozyten hervorgehoben, einerseits durch die genetische Analyse von Einzelpersonen, die an Cholesterinstoffwechsel- Störungen leiden, andererseits durch einige klinische Studien, die die Effekte von diätetischen Pflanzensterolen (phytosterols) oder spezifischen Proteininhibitoren auf wesentliche Komponenten der Cholesterinaufnahme-Systeme untersucht haben. ..

Social values in context: a study of the European knowledge society

This thesis investigates how social values align with changing patterns of economic development, work and quality of life in the European knowledge society. Conceptually, the thesis draws upon Richard Florida's Theory of the Creative Class (2002) and Human Values Theory as developed by Shalom Schwartz (1992). The research combines different methodological approaches and is structured in three parts. The first study involves a secondary data analysis of the European Social Survey that includes Schwartz's value inventory and other value related items. It aims at mapping the values of Florida's three key occupational groups: knowledge, service and manufacturing workers. While manufacturing workers were found to be distinct from knowledge and service workers, the latter two categories were rather similar. In addition, a mixture of liberal and traditional values characterised knowledge workers' value systems. Little empirical support was found for Schwartz's circumplex structure of values. The second part of the thesis, using two split-ballot experiments and cognitive interviews, explores the role of context in the conceptualisation and study of values. Drawing on the concept of 'behavioural spheres' (Kluckhohn and Strodtbeck, 1961), the operation of values in the familial, recreational and occupational sphere is examined. The findings show that many values demonstrated context specificity. In-depth interviews with Greek and British knowledge and service workers constitute the third and final study. I examine how workers' valuing processes delineate their creative endeavours to construct the meaning of work and good life, as embedded in the wider societal, economic, political and work contexts. Creativity focuses on how workers, create value meanings and enact values, combine different roles, make sense of their living and the world and deal with adversities. It was shown that the ability to transform work into a meaningful activity is not restricted to knowledge workers. The findings altogether did not corroborate Florida's proposal of an emerging creative class with distinct value orientations and Schwartz's model of a structure of universal values, captured in a set of binary oppositions. A range of challenges for policy making in the knowledge society is implied when authenticity rather than creativity - as defined by Florida- was found to delineate the European work ethos

Μελέτη της in vitro κυτταρολυτικής δραστικότητας των ΝΚ κυττάρων ασθενών πασχόντων από Μυελικές Κακοήθειες

Στην παρούσα προοπτική μελέτη εκτιμήθηκε η συσχέτιση μεταξύ της ΝΚ κυτταροτοξικής δραστικότητας, των Μυελικών Κατασταλτικών κυττάρων (Myeloid Derived Suppressor cells - MDSCs) και των Τ-ρυθμιστικών κυττάρων (T-Regulatory cells – Tregs), ως προς τη διάρκεια της ανταπόκρισης και την ολική επιβίωση, ασθενών πασχόντων από υψηλού κινδύνου Μυελοδυσπλαστικό σύνδρομο (ΜΔΣ) ή ολιγοβλαστική Οξεία Μυελογενή Λευχαιμία (ΟΜΛ) που λάμβαναν θεραπεία με τον υπομεθυλιωτικό παράγοντα 5-Αζασυτιδίνη. Ο απώτερος σκοπός της μελέτης ήταν η αναγνώριση πρώιμων βιοδεικτών με προγνωστική σημασία ως προς την συνολική ανταπόκριση των ασθενών αυτών στη χορηγούμενη θεραπεία. Οι ασθενείς που συμμετείχαν στην παρούσα μελέτη είχαν ήδη λάβει τουλάχιστον τρείς κύκλους θεραπείας με τον υπομεθυλιωτικό παράγοντα 5-Αζασυτιδίνη. Η in vitro προσδιορισμένη ΝΚ-κυτταροτοξικότητα σε αυτή την ομάδα των ασθενών έχει προγνωστική αξία ως προς τη διάρκεια της ανταπόκρισης και ως προς την ολική επιβίωση, οι ασθενείς που επιδείκνυαν υψηλή ΝΚ-κυτταροτοξικότητα παρουσίαζαν μακρύτερη επιβίωση και μακρύτερη διάρκεια ανταπόκρισης σε σύγκριση με τους ασθενείς που επιδείκνυαν χαμηλή ΝΚ-κυτταροτοξικότητα. Οι πληθυσμοί των ανοσορρυθμιστικών κυττάρων MDSCs και Tregs στο περιφερικό αίμα ασθενών μετά βραχεία έκθεση σε 5-Αζασυτιδίνη, δε διέφεραν στατιστικώς σημαντικά σε σύγκριση με τον πληθυσμό των υγιών μαρτύρων. Σύμφωνα με τα αποτελέσματα της μελέτης μας, η θεραπευτική δράση της 5-Αζασυτιδίνης διενεργείται, τουλάχιστον μερικώς, μέσω ανοσορρυθμιστικής επίδρασης του παράγοντα αυτού. Με βάση την πρόσφατη αναζήτηση της βιβλιογραφίας, η μελέτη αυτή αποτελεί την πρώτη δημοσιευμένη μελέτη που καταγράφει θετική συσχέτιση μεταξύ της ΝΚ-κυτταροτοξικότητας και της ολικής επιβίωσης ασθενών υπό 5-Αζασυτιδίνη.In our study, we prospectively examined the correlation between NKcytotoxic activity, Myeloid-derived Suppressor cells (MDSCs) and TRegulatory cells (Tregs), with the duration of response (DOR) and the overall survival (OS) of patients with high-risk myelodysplastic syndrome (MDS) and oligoblastic acute myeloid leukaemia (AML) treated with 5-Αzacytidine (AZA), with the aim to identify early biomarkers predictive of the final outcome. Patients enrolled at the study had already received at least three cycles of 5-Αzacytidine treatment. Peripheral blood NKcytotoxicity at completion of chemotherapy is predictive of DOR and OS; AZA-treated patients with high NK-cytotoxicity survived longer and response to treatment was sustained for a longer period than patients with low NK-cytotoxicity. In contrast, numbers of MDSCs and Tregs in the peripheral blood (PB) of patients after a short exposure to 5-Αzacytidine were not significantly different from normal donors. The results of our study suggest that the therapeutic activity of 5-Αzacytidine is at least partly mediated by an immunomodulatory effect. To our knowledge, this is the first study that shows a positive correlation between NK-cytotoxicity and OS of AZA-treated patients

Antineutrophil Cytoplasmic Antibodies Testing in a Large Cohort of Unselected Greek Patients

Objective. To retrospectively evaluate ANCA testing in a cohort of unselected Greek in- and outpatients. Methods. In 10803 consecutive serum samples, ANCA were tested by indirect immunofluorescence (IIF) and ELISA. ELISA in inpatients was performed only on IIF positive sera. Results. Low prevalence (6.0%) of IIF positive samples was observed. Among these samples, 63.5% presented perinuclear (p-ANCA), 9.3% cytoplasmic (c-ANCA) and 27.2% atypical (x-ANCA) pattern. 16.1% of p-ANCA were antimyeloperoxidase (anti-MPO) positive, whereas 68.3% of c-ANCA were antiproteinase-3 (anti-PR3) positive. Only 17 IIF negative outpatients' samples were ELISA positive. ANCA-associated vasculitides (AAV), connective tissue disorders and gastrointestinal disorders represented 20.5%, 23.9%, and 21.2% of positive results, respectively. AAV patients exhibited higher rates of MPO/PR3 specificity compared to non-AAV (93.8% versus 8%). Conclusions. This first paper on Greek patients supports that screening for ANCA by IIF and confirming positive results by ELISA minimize laboratory charges without sacrificing diagnostic accuracy

Η παραπλανητική διαφήμιση υπό το δίκαιο του αθέμιτου ανταγωνισμού και της προστασίας του καταναλωτή.

Αντικείμενο αυτής της μελέτης είναι η εξέταση της παραπλανητικής διαφήμισης και της προστασίας, που παρέχει στο καταναλωτικό κοινό ο ενωσιακός και ο εθνικός νομοθέτης μέσω της εξέτασης του νομικού πλαισίου, στο οποίο αυτή εντάσσεται. Στο πρώτο μέρος, της παρούσας εργασίας, θα παρουσιαστεί η έννοια της παραπλανητικής διαφήμισης, το νομοθετικό πλαίσιο που τη ρυθμίζει, και ειδικότερα η προστασία της στο ν. 146/1914 για την προστασία του αθέμιτου ανταγωνισμού, και συγκεκριμένα αναλύονται διεξοδικά τα άρθρα 1 και 3 του ν. 146/1914. Στο δεύτερο μέρος αναλύεται, η ρύθμιση της παραπλανητικής διαφήμισης στο ν. 2251/1994 για την προστασία των καταναλωτών. Τέλος στο τρίτο μέρος γίνεται μια σύγκριση των δύο νομοθετημάτων τα οποία, όπως θα αναλυθεί κατωτέρω παρά το ότι έχουν το ίδιο ρυθμιστικό αντικείμενο, επικεντρώνονται σε διαφορετικές όψεις του ίδιου νομίσματος, χωρίς όμως να τελούν σε σχέση γενικού προς ειδικό, αλλά αντίθετα εφαρμόζονται παράλληλα. Το ζήτημα της παραπλανητικής διαφήμισης έχει απασχολήσει εδώ και δεκαετίες τον ενωσιακό και εθνικό νομοθέτη, με αποτέλεσμα το νομικό της πλαίσιο να καθίσταται όλο και ευρύτερο. Ο Έλληνας νομοθέτης, μάλιστα, στο ζήτημα της παραπλανητικής διαφήμισης, έχει ακολουθήσει -με ελάχιστες εξαιρέσεις- πιστά και ορθά το ευρωπαϊκό πρότυπο της Οδηγίας 2005/29/ΕΚ, ενώ έχει αξιοποιήσει σε μεγάλο βαθμό τις δυνατότητες του άρθρου 11 αυτής σχετικά με τις επιβληθείσες κυρώσεις, προκειμένου η προστασία του καταναλωτή να επιτυγχάνεται μέσα από πλείστες διαδικασίες, ο έλεγχος της διαφήμισης δε να γίνεται από διαφόρους φορείς, ανήκοντες όχι μόνο στη δικαστική αλλά και στην εκτελεστική εξουσία.The purpose of this study is to examine misleading advertising and the unfair competition law and consumer protection law. In the first part of this study, the scope of misleading advertising will be presented, the legal framework that regulates it, and in particular its protection in law 146/1914 for the protection of unfair competition, and specifically articles 1 and 3 are analyzed in detail. of Law 146/1914. The second part analyzes the regulation of misleading advertising in Law 2251/1994 for the protection of consumers. Finally, in the third part, a comparison is made between the two legislations which, as will be analyzed below, despite having the same regulatory object, focus on different aspects of the same currency, but without being in a general to specific relation, but instead are applied in parallel

Collective victimhood in populist media about Brexit: rage against the machine?

This paper outlines an ongoing qualitative study in social psychology, with a pilot study completed and the main study currently at the data analysis stage. We examine how collective and competitive victimhood are invoked in populist rhetoric and media coverage of the United Kingdom’s departure from the European Union (Brexit). Brexit has been portrayed by its proponents as a project on behalf of ordinary British people against an out-of-touch liberal elite and a malevolent European Union (EU), with the opposing campaign to remain in the EU commonly characterised as an alarmist “project fear” (see Bartholomew, 2017; Durrheim et al., 2018; Forsyth, 2016; Malik, 2018). This populist idea of ordinary people as victims of manipulative and mendacious elites seems to relate to social-psychological work on collective and competitive victimhood (Bar-Tal et al., 2009; Noor et al., 2008a, 2008b, 2012; Vollhardt et al., 2014). According to this account, victimhood can be used as political capital to justify grievances and intergroup conflict. Research on this topic has mostly used quantitative methods, but first attempts have been made to use qualitative methods to show rhetorical functions of collective and competitive victimhood (McNeill et al., 2017). Building on these theoretical and methodological foundations, we use thematic analysis and discourse analysis to show how victimhood is mobilised in British media to garner support for Brexit, and how this connects with concepts such as collective relative deprivation (e.g. Abrams & Grant, 2012; Runciman, 1966) and relative gratification (Dambrun et al., 2006; Guimond & Dambrun, 2002; Jetten et al., 2015). In doing so, we contribute to a social-psychological perspective on Brexit, develop further the concepts of collective and competitive victimhood, and connect the micro-level of language used in the media sphere to the macro-level of populist movements in democratic societies

Short Tandem Repeats Loci in Parentage Testing

The need for confirmation or exclusion of biological father and / or biological mother is a social phenomenon, which is imposed by socio-economic and, sometimes, by moral-psychological factors. Modern science has significantly contributed to solving this problem, as many medical methods have been applied for this purpose. Biological markers that have been conducted for distinguishing between individuals were the human ABO blood groups, the Rh, MNS, Duffy, Kidd, and Kell systems, as well as the human leukocyte antigens (HLA) system. For a long time theHLA testing represented the standard testing in forensic genetics, but, due to the linkage disequilibrium and the predominance of certain HLA alleles and as the demand for parentage investigations is rapidly increasing during the recent years, this serological era has been replaced by molecular markers through the introduction of “DNA profiling”, which is based on polymorphisms of short tandem repeats (STRs) loci. Nowadays, “DNA profiling” by analysis of STR loci is the method of choice for human identification and parentage investigations. This technique is the most informative, accurate, robust, rapid, cost-effective method of genotyping and has worldwide acceptance in the courts, as the probability of parentage will typically be greater than 99.99999%

Two-Stage Priming of Allogeneic Natural Killer Cells for the Treatment of Patients with Acute Myeloid Leukemia: A Phase I Trial

Human Natural Killer (NK) cells require at least two signals to trigger tumor cell lysis. Absence of ligands providing either signal 1 or 2 provides NK resistance. We manufactured a lysate of a tumour cell line which provides signal 1 to resting NK cells without signal 2. The tumor-primed NK cells (TpNK) lyse NK resistant Acute Myeloid Leukemia (AML) blasts expressing signal 2 ligands. We conducted a clinical trial to determine the toxicity of TpNK cell infusions from haploidentical donors. 15 patients with high risk AML were screened, 13 enrolled and 7 patients treated. The remaining 6 either failed to respond to re-induction chemotherapy or the donor refused to undergo peripheral blood apheresis. The conditioning consisted of fludarabine and total body irradiation. This was the first UK trial of a cell therapy regulated as a medicine. The complexity of Good Clinical Practice compliance was underestimated and led to failures requiring retrospective independent data review. The lessons learned are an important aspect of this report. There was no evidence of infusional toxicity. Profound myelosuppression was seen in the majority (median neutrophil recovery day 55). At six months follow-up, three patients treated in Complete Remission (CR) remained in remission, one patient infused in Partial Remission had achieved CR1, two had relapsed and one had died. One year post-treatment one patient remained in CR. Four patients remained in CR after treatment for longer than their most recent previous CR. During the 2 year follow-up six of seven patients died; median overall survival was 400 days post infusion (range 141–910). This is the first clinical trial of an NK therapy in the absence of IL-2 or other cytokine support. The HLA-mismatched NK cells survived and expanded in vivo without on-going host immunosuppression and appeared to exert an anti-leukemia effect in 4/7 patients treated