Sekretarz króla Stanisława Leszczyńskiego – agent czy wierny sługa

Celem niniejszego opracowania jest przedstawienie sylwetki osobistego (przybocznego) sekretarza króla Stanisława Leszczyńskiego w Lotaryngii zarówno jako agenta, jak i wiernego sługi. Podstawę źródłową do napisania tejże pracy stanowią materiały pochodzące z Bibliotheque Municipale de Nancy i polskich archiwów

Analysis of genes involved in response to doxorubicin and a GD2 ganglioside-specific 14G2a monoclonal antibody in IMR-32human neuroblastoma cells

Neuroblastoma is the most common extra-cranial solid tumor of childhood and it is characterized by the presence of a glycosphingolipid, GD2 ganglioside. Monoclonal antibodies targeting the antigen are currently tested in clinical trials. Additionally, several research groups reported results revealing that ganglioside-specific antibodies can affect cellular signaling and cause direct cytotoxicity against tumor cells. To shed more light on gene expression signatures of tumor cells, we used microarrays to analyze changes of transcriptome in IMR-32 human neuroblastoma cell cultures treated with doxorubicin (DOX) or a mouse monoclonal antibody binding to GD2 ganglioside 14G2a (mAb) for 24 h. The obtained results highlight that disparate cellular pathways are regulated by doxorubicin and 14G2a. Next, we used RT-PCR to verify mRNA levels of selected DOX-responsive genes such as RPS27L, PPM1D, SESN1, CDKN1A, TNFSF10B, and 14G2a-responsive genes such as SVIL, JUN, RASSF6, TLX2, ID1. Then, we applied western blot and analyzed levels of RPS27L, PPM1D, sestrin 1 proteins after DOX-treatment. Additionally, we aimed to measure effects of doxorubicin and topotecan (TPT) and 14G2a on expression of a novel human NDUFAF2 gene encoding for mimitin protein (MYC-induced mitochondrial protein) and correlate it with expression of the MYCN gene. We showed that expression of both genes was concomitantly decreased in the 14G2a-treated IMR-32 cells after 24 h and 48 h. Our results extend knowledge on gene expression profiles after application of DOX and 14G2a in our model and reveal promising candidates for further research aimed at finding novel anti-neuroblastoma targets

The influence of ADAM17 and ADAM10 on TNF shedding and NO secretion. The influence of silencing of ADAM17 on intracellular signal transduction.

ADAM17 i ADAM10 należą do rodziny metaloproteaz dysintegrynowych. Uczestniczą one w ścinaniu licznych cytokin, czynników wzrostu i ich receptorów z błony komórkowej i z tego powodu wywierają ogromny wpływ na regulację funkcjonowania układu immunologicznego, procesów wzrostu i różnicowania komórek.Celem niniejszej pracy było uzyskanie klonów linii P388D1 z obniżoną ekspresją ADAM17 i ADAM10 poprzez transfekcję komórek plazmidem z odpowiednim shRNA i selekcję klonów przy użyciu higromycyny i genetycyny. Wyciszenie ekspresji docelowych genów zostało sprawdzone techniką PCR w czasie rzeczywistym i potwierdzone metodą Northern Blotting. Na podstawie tych wyników, do dalszych eksperymentów in vitro wybrano klony charakteryzujące się najniższym poziomem ekspresji ADAM17 i ADAM10.W drugiej części pracy skupiono się na zbadaniu funkcji ADAM17 i ADAM10. Wyniki przeprowadzonych analiz potwierdziły rolę ADAM17 w stymulowanym przez PMA ścinaniu TNFalpha. Ponadto, wyniki pokazują, ze wyciszenie ekspresji ADAM17 prowadzi do znacznego zahamowania produkcji NO. Przeprowadzone doświadczenia wskazują, że ADAM10 nie bierze udziału w ścinaniu TNFalpha i wydzielaniu NO, a główną rolę w tych procesach odgrywa ADAM17.Ostatecznie podjęto się próby odpowiedzi na pytanie czy wyciszenie sekretazy ADAM17 wpływa na wewnątrzkomórkowy przekaz sygnału. Pokazano, że ścieżki sygnalizacyjne prowadzące do aktywacji czynnika transkrypcyjnego AP-1 mogą być zaangażowane w regulację transkrypcji genów związanych z układem immunologicznym i stanem zapalnym w tym iNOS, IL-6. Wykazano, że aktywacja czynników transkrypcyjnych STAT1 i NFkappaB jest niezależna od stopnia wyciszenia ADAM17.ADAM17 and ADAM10 are members of the ADAM (a disintegrin and metalloproteinase domain) family. They are able to shed numerous cytokines, growth factors and their receptors from cell membrane and because of that they have great involvement in the regulation of immune system functioning, processes of cell growth and differentiation. The aim of this study was to obtain stably silenced-ADAM17 and ADAM10 clones of P388D1 cells via transfection of the cells with suitable shRNA-codnig plasmid and subsequent selection with hygromycin and geneticin. Silencing of target genes expression was checked with Real time Quantitative PCR and Northern Blotting methodes. On the basis of these results, clones characterized by the lowest level of ADAM17 and ADAM10 were chosen to further in vitro experiments.The second part of the work focused on ADAM17 and ADAM10 functions. The outcome of the analysis confirmed the role of ADAM17 in PMA-induced shedding of TNFalpha. Furthermore, results demonstrate that silencing of ADAM17 resulted in a significant inhibition of NO production. In these experiments ADAM10 does not take part in TNFalpha shedding and NO secretion and it is ADAM17, which plays a major role in these processes.Finally, the attempt was made to answer the question if silencing of ADAM17 secretase has the influence on intracellular signal transduction. It was shown that signalling pathways leading to activation of AP-1 transcription factor can be involved in regulation of transcription of immune response and inflammatory genes e.g. iNOS, IL-6. It was confirmed that there is no correlation between the level of ADAM17 expression and activation of NFkappaB and STAT1

Présence d’André Le Nôtre dans les jardins du palais de Franciszek Salezy Potocki à Krystynopol au milieu du xviiie siècle

André Le Nôtre, « maître de l’illusion et de la splendeur », a laissé de grandes œuvres parmi lesquelles les jardins de Versailles. Ceux-ci avaient été conçus comme un acte créateur, considéré comme un symbole du pouvoir absolu et de la puissance du roi, qui avec le temps a perdu de son lustre en France. Toutefois, les principes généraux des jardins de Le Nôtre, souvent repris et imités, ont été très appréciés dans de nombreux pays européens, y compris en Pologne au milieu du xviiie siècle. L’objectif de cet article est de présenter le style du jardin à la française comme un reflet visuel et intemporel de la puissance aristocratique de la famille Potocki. Voulant conférer une certaine splendeur à son pouvoir nobiliaire, Franciszek Salezy Potocki, surnommé « le petit roi de Ruthénie », décida de se bâtir à Krystynopol, en Ruthénie, une nouvelle résidence consistant en un palais et un jardin parmi les plus raffinés de la République des Deux Nations au milieu du xviiie siècle. L’ensemble du projet, réalisé selon les plans de Pierre Ricaud de Tirregaille en 1757-1760, rappelle véritablement les palais royaux de type français, avec deux cours, un château, des ailes et des annexes à disposition axiale qui se prolongent dans la composition du jardin avec une cascade et des fontaines. La résidence de Potocki à Krystynopol avec ses jardins uniques, immortalisée par le dessin et l’aquarelle, joue en outre une fonction très importante dans la vie sociale et économique de son propriétaire.André Le Nôtre, ‘master of illusion and splendour’, is remembered for a number of great works, including the gardens of Versailles. These were conceived as an act of creation, a symbol of absolute power and royal might, which, over time, had lost their lustre in France. The main principles of Le Nôtre’s gardens, often imitated, remained popular in many European countries, however, including the Polish-Lithuanian Commonwealth in the mid-eighteenth century. This article discusses the French style of garden design as a timeless, visual representation of the aristocratic grandeur of the Potocki family. To enhance the splendour of his noble prestige, Franciszek Salezy Potocki, the ‘Little King of Ruthenia’, built a new residence in Krystynopol in Ruthenia, one of the most elegant palace-garden complexes in the Polish-Lithuanian Commonwealth in the mid-eighteenth century. The whole project, constructed to the designs of Pierre Ricaud de Tirregaille in the years 1757-1760, is strongly reminiscent of a royal residence of the French type, with two courtyards, a palace building, wings and annexes, whose layout extended into composition of the garden with a cascade and fountains. The Potocki residence in Krystynopol, together with its unique gardens, depicted in drawings and watercolours, also played a very important role in its owner’s social and economic life

The first academic discourse about dwarfism in the eighteenth century on the example of the dwarf of Lunéville

In the conventional wisdom of the Enlightenment the topic of dwarfism as a medical disorder was not present. Dwarfs were sought after for and highly valued at European aristocratic and royal courts, but they stayed at the margins of social life because of their body build. The aim of this article is to discuss the first academic research connected with dwarfism on the example of King Stanislaw Leszczynki’s dwarf in Lunéville. Nicolas Ferry, known as Bébé, like other dwarfs during the trend of that time was a mascot of courtiers, up to his death at the age of 23 by the King’s side in the palace. The King, upset by the death of his prematurely aged pupil Bébé, ordered his doctors to examine the corpse. Part of the research material was sent to Paris to the Cabinet of Natural History (Cabinet d’Histoire Naturelle du Roi) of Count de Buffon, who started an examination. The case of the dwarf Bébé was described in the series Histoire naturelle... of 12 volumes in the section onquadrupeds. From the point of view of cultural controversies about dwarfism – nowadays treated as a disease in the medical model of disability – the case is an important question because it shows the beginning of the process of departing from the beliefs of the eighteenth century towards the first anatomical academic research

Pierwszy akademicki dyskurs o karłowatości w xviii wieku na przykładzie karła z Luneville

In the conventional wisdom of the Enlightenment the topic of dwarfi sm as a medical disorder was not present.Dwarfs were sought after for and highly valued at European aristocratic and royal courts, but they stayed at the margins of social life because of their body build. The aim of this article is to discuss the fi rst academic research connected with dwarfi sm on the example of King Stanislaw Leszczynki’s dwarf in Lunéville. Nicolas Ferry, known as Bébé, like other dwarfs during the trend of that time was a mascot of courtiers, up to his death at the age of 23 by the King’s side in the palace. The King, upset by the death of his prematurely aged pupil Bébé, ordered his doctors to examine the corpse. Part of the research material was sent to Paris to the Cabinet of Natural History (Cabinet d’Histoire Naturelle du Roi) of Count de Buff on, who started an examination. The case of the dwarf Bébé was described in the series Histoire naturelle... of 12 volumes in the section on quadrupeds. From the point of view of cultural controversies about dwarfi sm – nowadays treated as a disease in the medical model of disability – the case is an important question because it shows the beginning of the process of departing from the beliefs of the eighteenth century towards the fi rst anatomical academic research.W okresie oświecenia karłowatości nie uznawano za zaburzenie medyczne. Karły były poszukiwane i cenione na europejskich dworach arystokratycznych i królewskich, ale pozostały na marginesie życia społecznego z powodu budowy ciała. Celem tego artykułu jest omówienie pierwszych badań naukowych związanych z karłowatością na przykładzie karła na dworze króla Stanisława Leszczyńskiego w Lunéville. Nicolas Ferry, znany jako Bébé,podobnie jak inne karły w tamtym okresie, był maskotką dworzan i mieszkał aż do śmierci w wieku dwudziestu trzech lat u boku króla w pałacu. Król, zaniepokojony przedwczesną śmiercią Bébé, nakazał lekarzom zbadanie zwłok. Część materiałów badawczych wysłano do Paryża do Gabinetu Historii Naturalnej (Cabinet d’Histoire Naturelle du Roi) hrabiego de Buff ona, który rozpoczął badania. Przypadek karła Bébé został opisany w serii Histoire naturelle... w 12 tomie w części dotyczącej czworonogów. Z punktu widzenia kontrowersji kulturowych na temat karłowatości (obecnie traktowanej jako choroba w medycznym modelu niepełnosprawności) opisywany przypadek ma istotne znaczenie, ponieważ pokazuje początek procesu odchodzenia w XVIII wieku porzucono wiarę w mity i przesądy dotyczące karłów na rzecz anatomicznych badań akademickic

Patrimoine culturel sarmate dans l’espace social du Duché de Lorraine et de Bar sous le règne du roi Stanisław Leszczyński (1737-1766), expression de l’identité culturelle polonaise

The aim of the article is to discuss the Sarmatian cultural transfer into the social space of Lor-raine as a manifestation of the Polish cultural identity of the king of Poland, duke of Lorraine and Bar, Stanislaus Leszczynski, a European and a citizen of the world. Leszczynski’s prolific contributions in his new homeland had its roots in the Sarmatian culture, one in which he grew up and which became ingrained in his consciousness. Through the Polish monarch and his Polish entourage, elements of Polish cultural identity—profoundly anchored in the Sarmatian background—began to permeate into the social space of the new homeland of Lorraine.The aim of the article is to discuss the Sarmatian cultural transfer into the social space of Lorraine as a manifestation of the Polish cultural identity of the king of Poland, duke of Lorraine and Bar, Stanislaus Leszczynski, a European and a citizen of the world. Leszczynski’s prolific contributions in his new homeland had its roots in the Sarmatian culture, one in which he grew up and which became ingrained in his consciousness. Through the Polish monarch and his Polish entourage, elements of Polish cultural identity—profoundly anchored in the Sarmatian background—began to permeate into the social space of the new homeland of Lorraine.  The aim of the article is to discuss the Sarmatian cultural transfer into the social space of Lor-raine as a manifestation of the Polish cultural identity of the king of Poland, duke of Lorraine and Bar, Stanislaus Leszczynski, a European and a citizen of the world. Leszczynski’s prolific contributions in his new homeland had its roots in the Sarmatian culture, one in which he grew up and which became ingrained in his consciousness. Through the Polish monarch and his Polish entourage, elements of Polish cultural identity—profoundly anchored in the Sarmatian background—began to permeate into the social space of the new homeland of Lorraine