Hortuli animae iz let 1516 in 1548 v Narodni in univerzitetni knjižnici v Ljubljani: predreformacijski molitvenik in njegova luteranska transformacija

The collection of rare prints at the National and University Library of Ljubljana contains two small printed prayer books entitled Hortulus animae. One is from 1516 and the other from 1548, and both are embellished with numerous woodcut illustrations. On closer inspection, the similarities between the booklets soon vanish: the older one belongs to the golden age of pre-Reformation prayer books of the first two decades of the sixteenth century, and the second one to the Reformation. Nevertheless, both examples have so far been ignored by scholars. The Latin prayer book dated 1516 was published in Mainz by Johann Schöfer. It belongs to the important and numerous group of pre-Reformation prayer books, among which Hortulus animae was most successful. This type derives from books of hours, with adjustments to central European devotional practices. Hortulus animae is a compendium of diverse devotional texts designed to equip Christians for every situation in which they might need divine assistance. An important role was also played by numerous illustrations, as proven by some prayers that explicitly demand recitation before a specific image (the prayers of St. Gregory the Great and St. Anne). The importance of these booklets is confirmed by the importance of some of the artists that provided illustrations, such as Albrecht Dürer, Hans Burgkmair the Elder, and Hans Holbein the Younger. The illustrations in the Ljubljana prayer book were all executed by a single master, which was not common for this type of publication. His name and his other works are unknown, although the quality of his woodcuts surpasses many in other series used at this time. The special value of this prayer book also lies in numerous traces left by its owners, the most impressive being the drawing of the coat of arms on the back cover. The second Hortulus animae with German text was published in Wittenberg in 1548 by the important Protestant publisher Georg Rhau. The texts, partly written by Martin Luther and Philipp Melanchthon, show crucial differences from their pre-Reformation predecessor. Although richly illustrated with Lucas Cranach’s pre-Reformation woodcuts for a Wittenberg relics collection book from 1509, their meaning did not remain the same. Luther was very aware of the power of images, specially over the less educated. His teachings are perfectly expressed in this prayer book. The images of saints are limited to Christ’s family, the twelve apostles, and John the Baptist, and several points in the text are equipped with a warning against idolatry. The smaller group of illustrations depicting specific Reformation subjects was contributed by a younger anonymous artist known only by his monogram, A W. Each in its specific historical context, both prayer books are therefore a valuable document of pre-Reformation and Reformation piety in central Europe of the first half of the sixteenth century

Tumor vaccine composed of C-class CpG oligodeoxynucleotides and irradiated tumor cells induces long-term antitumor immunity

<p>Abstract</p> <p>Background</p> <p>An ideal tumor vaccine should activate both effector and memory immune response against tumor-specific antigens. Beside the CD8+ T cells that play a central role in the generation of a protective immune response and of long-term memory, dendritic cells (DCs) are important for the induction, coordination and regulation of the adaptive immune response. The DCs can conduct all of the elements of the immune orchestra and are therefore a fundamental target and tool for vaccination. The present study was aimed at assessing the ability of tumor vaccine composed of C-class CpG ODNs and irradiated melanoma tumor cells B16F1 followed by two additional injections of CpG ODNs to induce the generation of a functional long-term memory response in experimental tumor model in mice (i.p. B16F1).</p> <p>Results</p> <p>It has been shown that the functional memory response in vaccinated mice persists for at least 60 days after the last vaccination. Repeated vaccination also improves the survival of experimental animals compared to single vaccination, whereas the proportion of animals totally protected from the development of aggressive i.p. B16F1 tumors after vaccination repeated three times varies between 88.9%-100.0%. Additionally, the long-term immune memory and tumor protection is maintained over a prolonged period of time of at least 8 months. Finally, it has been demonstrated that following the vaccination the tumor-specific memory cells predominantly reside in bone marrow and peritoneal tissue and are in a more active state than their splenic counterparts.</p> <p>Conclusions</p> <p>In this study we demonstrated that tumor vaccine composed of C-class CpG ODNs and irradiated tumor cells followed by two additional injections of CpG ODNs induces a long-term immunity against aggressive B16F1 tumors.</p

Recepcija Poslednje sodbe münchenskega slikarja Christopha Schwarza in odmevi Michelangelove Poslednje sodbe na Slovenskem

The study is dedicated to the interesting example of the reception of a specific printed model in Slovenian lands at the time of Counter-Reformation. The copperplate engraving of the Last Judgement by Jan Sadeler I around the year 1590 enjoyed great popularity throughout Central Europe, but semed to gain further religious and political connotations in this region. The print reproduces a now lost painting by Munich painter Christoph Schwarz, made in 1580's for Duchess Renata of Lorraine, wife of William V, Duke of Bavaria, and was notably influenced by Michelangelo's Last Judgement mural in the Sistine Chapel. The earliest known copies and reflections on the print can be found at the Graz court and its close circle. The Slovenian lands were at the time a part of a separate political entity of Inner-Austria, with Graz as its capital. Two copies of the painting in Slovenia after the print can be interpreted as sign of loyalty to ruling Habsburg dynasty, which had close political, religious, and family ties with Munich court. The most notable example can be found on the ceiling in the “Lutheran cellar” in Sevnica, probably painted in the first two decades of the 17th century under the patronage of Baron Inocenz Moscon, an important Styrian nobleman and adviser to Archduke Ferdinand III. The second example can be more loosely linked with one of the leading figures of the local Counter-Reformation, Tomaž Hren, Bishop of Ljubljana, in the parish church of Grad above Stari trg by Slovenj Gradec, possibly from the first third of the century. A further two examples can be interpreted as more common usage of Sadeler's print, without any political connotations. Only some details from the print were copied on the Last Judgment mural in the parish church of Ormož from 1630's, and on the panel painting in pilgrimage church dedicated to Virgin Mary in Puščava in Pohorje from the end of the century, which even features additional elements from Michelangelo's Sistine fresco.Študija je posvečena zanimivemu primeru recepcije specifične grafične predloge na Slovenskem v času protireformacije. V Srednji Evropi izjemno priljubljeni bakrorez s Poslednjo sodbo, ki ga je ok. leta 1590 izdelal Jan Sadeler st., je v tej regiji, kot kaže, dobil še posebne religiozne in politične konotacije. Grafični list reproducira danes izgubljeno sliko münchenskega slikarja Christopha Schwarza, nastalo v 80. letih 16. stoletja za vojvodinjo Renato Lotarinško, soprogo bavarskega vojvode Vilijema V. Slika je nastala pod občutnim vplivom Michelangelove Poslednje sodbe v Sikstinski kapeli. Prve kopije in reflekse po grafiki lahko najdemo na graškem dvoru in v njegovem tesnem krogu – slovenske dežele so bile v tem obdobju namreč del posebne politične tvorbe, imenovane Notranja Avstrija, s prestolnico v Gradcu. Dva slovenska primera lahko interpretiramo kot znak zvestobe vladajoči habsburški dinastiji, ki je imela tesne politične, religiozne in družinske vezi z münchenskim dvorom. Najpomembnejši primer najdemo v t. i. Lutrovski kleti v Sevnici, ki je bila najverjetneje v prvih dveh desetletjih 17. stoletja poslikana po naročilu Inocenca barona Moscona, pomembnega štajerskega plemiča in svetovalca nadvojvode Ferdinanda III. Drugi primer lahko sicer manj oprijemljivo povežemo z eno vodilnih lokalnih figur protireformacije, ljubljanskim škofom Tomažem Hrenom: poslikavo v župnijski cerkvi v Gradu nad Starim trgom pri Slovenj Gradcu, mogoče iz prve tretjine stoletja. S to grafiko lahko povežemo še dva zanimiva primera, vendar pri njiju ne moremo govoriti o tako močnih političnih konotacijah. Samo nekaj detajlov z grafike je bilo kopiranih na Poslednji sodbi iz ok. leta 1630 v župnijski cerkvi v Ormožu, prav tako pa tudi na tabelni sliki v romarski cerkvi Device Marije v Puščavi na Pohorju s konca stoletja, kjer lahko najdemo celo samostojen naslon na Michelangelovo sikstinsko fresko

Ponovno o stavbni zgodovini cerkve sv. Miklavža na Godešiču in ikonografiji poslikave njene zahodne fasade

The study sheds new light on the building history of the church of St Nicholas in Godešič and offers a new iconographic analysis of the painting on its western façade. The church was probably built in the 12th or 13th century and its choir in the early 16th century. An unknown Friulian painter painted the façade in the late 14th century and Jernej of Loka painted the presbytery before 1531. Previous research of the painting on the façade interpreted the preserved scenes as an extended Last Judgment. Above the entrance to the church, France Stele recognized the central group of the Last Judgment. Above it, he saw a depiction of Heaven with a figure of God the Father or Abraham, and to the right of it, a scene of the Wheel of Fortune. Alenka Vodnik sought the main source for the painting in apocryphal Apocalypse of Paul, and the scene with a wheel is thus supposed to represent the Wheel of Hell. A re-examination reveals different iconographic design: above the Last Judgment was the Coronation of the Virgin, on the right was a scene with St Catherine of Alexandria, and on the left a scene with St Nicholas.Študija vsebuje nove podatke o stavbni zgodovini cerkve sv. Miklavža na Godešiču in novo ikonografsko analizo poslikave na njeni zahodni fasadi. Cerkev je bila najbrž zgrajena v 12. ali 13. stoletju, prezbiterij pa na začetku 16. stoletja. Fasado je neznani furlanski slikar poslikal konec 14. stoletja, prezbiterij pa Jernej iz Loke pred letom 1531. V dosedanjih raziskavah o poslikavi fasade so bili ohranjeni prizori interpretirani kot razširjena Poslednja sodba. France Stele je nad vhodom v cerkev prepoznal osrednjo skupino Poslednje sodbe, nad njo upodobitev nebes s figuro Boga Očeta ali Abrahama, desno pa še prizor Kolo sreče. Alenka Vodnik je glavni vir za poslikavo iskala v apokrifni Pavlovi apokalipsi, pri čemer naj bi prizor s kolesom predstavljal Peklensko kolo. Ponovni pregled je pokazal drugačno zasnovo: nad Poslednjo sodbo je bilo Marijino kronanje, na desni je bil prizor s sv. Katarino Aleksandrijsko, na levi pa prizor s sv. Nikolajem

Detection of V600E Mutation in BRAF Gene

Mutacija V600E predstavlja več kot 90 % vseh opisanih mutacij v genu BRAF pri različnih vrstah tumorjev. Protein, ki nastane kot produkt onkogena BRAF z mutacijo V600E (BrafV600E), sproža nenehno signaliziranje prek signalne poti RAS-RAF-MAPK, kar povzroči številnejše delitve celice in njeno maligno transformacijo. Zato ima onkogen BrafV600E pomembno vlogo pri indukciji in napredovanju tumorja ter verjetno predstavlja zgodnji dogodek v procesu maligne transformacije. Po podatkih iz literature je čezmerno izražen v različnih vrstah solidnih tumorjev, kot so melanom, metastatski rak debelega črevesa in danke, papilarni rak ščitnice, rak ledvic (RCC), hepatocelularni karcinom (HCC), velikocelični rak pljuč (NSCLC) in serozni rak jajčnikov. Na Oddelku za molekularno diagnostiko smo uvedli metodo za določanje mutacije V600E v genu BRAF. Metoda temelji na PCR-pomnoževanju in uporabi specifičnih sond. Izkazala se je kot primerna za rutinsko diagnostiko. V primerjavi z neposrednim sekveniranjem, ki velja za zlati standard, sta bili njeni občutljivost in specifičnost 100-odstotni. Zaradi velike specifičnosti je zanesljiva za ločevanje med normalnim in mutiranim genotipom BRAF in je primerna za hitro rutinsko diagnostiko.The most common BRAF mutation, which accounts for more than 90% of all BRAF mutations described in different malignancies, is a glutamic acid for valin substitution at position 600 (V600E). BRAF gene carrying V600E mutation is termed BrafV600E oncogene. The product of BrafV600E is a protein which induces constitutive signaling in cells through hyperactivation of the RAS-RAF-MAPK pathway leading finally to increased cellular proliferation and malignant transformation. BrafV600E oncogene thus plays an important role in cancer induction and progression and is probably mutated early in the process of malignant transformation. According to the literature, BrafV600E oncogene is over-expressed in diverse human solid tumors: melanoma, colorectal carcinoma, papillary thyroid carcinoma, renal cell carcinoma (RCC), hepatocellular carcinoma (HCC), non-small cell lung cancer (NSCLC) and serous ovarian cancer. At the Department of Molecular Diagnostics, we introduced a method for the detection of V600E mutation in BRAF gene based on real-time PCR and on application of specific probes. The method is robust and convenient for routine diagnostics. Its sensitivity and specificity when determined in comparison to the results of direct sequencing are as high as 100%. Due to the high specificity, the method allows the discrimination between normal and mutated BRAF genotypes and is therefore suitable for fast and accurate routine diagnostics

Dokazovanje mutacij v genu BRCA1 z analizo talitvene krivulje produktov PCR

Rak dojke je z nekaj več kot 1000 novimi bolnicami na leto na prvem mestu po številu obolelih žensk za rakastimi boleznimi v Sloveniji. številka vključuje sporadične in dedne oblike raka na dojki. Dedne oblike raka na dojki so najpogosteje povezane z mutacijami v genih BRCA1 in BRCA2, zato se številni strokovnjaki s tega področja zavzemajo za genetsko testiranje bolnikov, pri katerih obstaja sum na dedno obliko bolezni. Testiranje bolnic/-kov in njihovih sorodnikov je dokaj težavno zaradi zahtevnosti metod genetskega testiranja, stroškov testiranja ter nezadostnega poznavanja in predvidevanja vseh možnih vplivov dokazane mutacije pri nastanku raka na dojki. V tem delu predstavljamo osnovne metodološke podatke za odkrivanje petih različnih mutacij v genu BRCA1 pri bolnicah/-kih s karcinomom dojke in njihovih sorodnikih. Mutacije 1806C>T, 300T>G, 300T>A, 310G>A, 5382insC določamo s polimerazno verižno reakcijo (PCR) v realnem času in analizo talitvene krivulje. Primerjava z neposrednim sekveniranjem je pokazala, da je uporabljena metoda dovolj občutljiva in hitra za dnevno rutinsko določanje mutacij v DNA, izolirani iz periferne krvi

Screening for melanoma susceptibility gene mutations in patients with familial cutaneous melanoma

Gensko testiranje za dedno obliko malignega melanoma kože na OI Ljubljana opravljamo od leta 2005. Izbor bolnikov za testiranje poteka v okviru genetskega svetovanja. Testiramo bolnike in njihove zdrave sorodnike, če sta v družini najmanj dva obolela člana, in bolnike s primarnimi multiplimi melanomi brez obremenjujoče družinske anamneze. Na oddelku za molekularno diagnostiko z metodo sekvenčne analize iščemo in določamo neznane točkovne mutacije ter manjše delecije in insercije v eksonih genov, povezanih z nastankom malignega melanoma kože: CDKN2A, CDK4 in MC1R. Do sedaj smo testirali 70 oseb: 40 bolnikov in njihovih zdravih sorodnikov iz 28 različnih družin, obremenjenih z družinsko anamnezo, ter 30 bolnikov s primarnimi multiplimi melanomi. Sekvenčna analiza genov, povezanih z dedno obliko malignega melanoma kože, je pokazala, da so mutacije CDKN2A p16INK4a pri bolnikih z družinsko anamnezo zelo pogoste (37,5 %). Mutacij CDKN2A p14ARF in CDK4 pri slovenskih bolnikih nismo našli.At the Institute of Oncology Ljubljana, Department of Molecular Diagnostics, genetic testing for familial cutaneous melanoma (CM) was started in 2005. The patients are selected according to the guidelines of genetic counseling for CM. The screening for melanoma susceptibility genes is performed in the patients and their healthy relatives from the families with at least two affected family members and in the patients with multiple primary CM without family history. The mutation screening for melanoma susceptibility genes – CDKN2A, CDK4 and MC1R is performed by direct sequencing. Altogether 70 patients and their healthy relatives (40 patients or their relatives selected from 28 families after considering their on family history and 30 patients with multiple primary CM) have been tested so far. Our results showed high prevalence of CDKN2A p16INK4a mutations in the patients with familial CM. In CDKN2A p14ARF and CDK4, no mutations were detected in Slovenian patients