Epigenetics of Reprogramming to Induced Pluripotency

Reprogramming to induced pluripotent stem cells (iPSCs) proceeds in a stepwise manner with reprogramming factor binding, transcription, and chromatin states changing during transitions. Evidence is emerging that epigenetic priming events early in the process may be critical for pluripotency induction later. Chromatin and its regulators are important controllers of reprogramming, and reprogramming factor levels, stoichiometry, and extracellular conditions influence the outcome. The rapid progress in characterizing reprogramming is benefiting applications of iPSCs and is already enabling the rational design of novel reprogramming factor cocktails. However, recent studies have also uncovered an epigenetic instability of the X chromosome in human iPSCs that warrants careful consideration

"Szent levél, melyet a mi Urunk Jézus Krisztus csudálatosképpen az ő földjén lakó népeihez küldött" : az Istenanya pokoljárása és más apokrif iratok egy ponyván

In der Studie beschäftigt sich die Verfasserin mit einem Kolportagenheft aus dem 19. Jahrhundert, das sowohl in ungarischer als auch in deutscher Sprache in Ungarn erschien. Die Kolportagenliteratur hatte ihre Blütezeit in dem 19. Jahrhundert, als sie die beliebte Lektüre verschiedener gesellschaftlicher Schichten war. Eine Art von dieser Literatur bilden die religiösen Kolportagenhefte, die biblischen Geschichten, Lieder, Gebete, moralische und andere religiöse Texte darstellen. Das untersuchte Heft enthält drei apokryphe Geschichten, die aus dem ersten Jahrtausend stammen. Der Heilige Brief darf - nach der Tradition - von Jesus bzw. Maria geschrieben worden sein, und er droht mit einer finsteren Zukunft, wenn die Menschen sich nicht verbessern. Der Traum von Maria ist eine sehr beliebte Geschichte, die sowohl in dem katholischen Westen als auch in dem orthodoxen Osten bekannt ist. Maria träumt über das Leiden von Jesus, der die Wahrhaftigkeit des Traums auch bestätigt. Die dritte Einheit des Heftes besteht aus der Höllenfahrt der Gottesmutter. Diese Geschichte kommt eindeutig aus slavischen Apokryphen und sie war bei den Katholiken völlig unbekannt. Die Höllenfahrt schildert eine Jenseitsvision von Maria, die in die Hölle von dem Erzengel Michael begleitet wurde. Sie schauen die verschiedenen Strafen an, und der Engel erklärt auch die Ursachen dafür. In diesem Kolportagenheft erscheint ein sehr komplexes Bild der Texten. Diese Geschichten verbinden mehrere Jahrhunderte, verschiedene Kulturen, Religionen und Traditionen miteinander

Über die Verehrung der 14 Nothelfer : Deutschsprachige Kleindrucke über die 14 Nothelfer

In diesem Beitrag werden vier Kleindrucke aus der Sammlung der Széchényi Nationalbibliothek vorgestellt, die das Thema der im deutschsprachigen Raum so populären Nothelfer behandeln. Die Hefte erschienen in einem Zeitraum von der zweiten Hälfte des 18. Jahrhunderts bis zum Anfang des 20. Jahrhunderts bei unterschiedlichen Druckereien. Ihre Leser kamen in erster Linie von den Ungarn-deutschen. Es wird untersucht, wie die Verehrung der Heiligen in diesen Texten erscheint. Vor der Vorstellung der einzelnen Hefte steht ein kurzer druckereihistorischer Überblick, der von der Inhaltsanalyse der Kleindrucke gefolgt wird

Hypoxia and HIF-1α promote lytic de novo KSHV infection

The impact of different stress conditions on the oncogenic Kaposi's sarcoma-associated herpesvirus (KSHV) primary infection that can occur in vivo remains largely unknown. We hypothesized that KSHV can establish a latency or lytic cycle following de novo infection, depending on the conditions of the cellular environment. Previous studies showed that hypoxia is a natural stress condition that promotes lytic reactivation and contributes to KSHV pathogenesis, but its effect on de novo KSHV infection is unknown. To test the effect of hypoxia on KSHV infection, we infected cells under normoxia and hypoxia, performed a comparative analysis of viral gene expression and viral replication, and tested chromatinization of the KSHV genome during infection. We found that hypoxia induces viral lytic gene expression and viral replication following de novo infection in several biologically relevant cell types, in which the virus normally establishes latency under normoxia. We also found that hypoxia reduces the level of repressive heterochromatin and promotes the formation of a transcriptionally permissive chromatin on the incoming viral DNA during infection. We demonstrate that silencing hypoxia-inducible factor-1 alpha (HIF-1 alpha) during hypoxia abrogates lytic KSHV infection, while the overexpression of HIF-1 alpha under normoxia is sufficient to drive lytic KSHV infection. Also, we determined that the DNA-binding domain and the N-terminal but not the C-terminal transactivation domain of HIF-1 alpha are required for HIF-1 alpha-induced lytic gene expression. Altogether, our data indicate that HIF-1 alpha accumulation, which can be induced by hypoxia, prevents the establishment of latency and promotes lytic KSHV infection following primary infection

Characterization of the Sterol 24-C-Methyltransferase Genes Reveals a Network of Alternative Sterol Biosynthetic Pathways in Mucor lusitanicus

The fungal membrane contains ergosterol instead of cholesterol, which offers a specific point of attack for the defense against pathogenic fungi. Indeed, most antifungal agents target ergosterol or its biosynthesis

Funkcionális kognitív nyelvészeti kutatás = Functional cognitive linguistics research

A kutatás a magyar nyelv funkcionális kognitív leírásának elméleti és módszertani kidolgozását és meghatározott nyelvi jelenségek részletes leírását végezte el alapkutatásként, a legfrissebb nemzetközi szakirodalommal diszkurzusban. A projekt konkrét eredményei. • Az Acta Linguistica Hungarica kettős tematikus száma, a 2009/4. és a 2010/1. szám, tizenegy tanulmánnyal. • Magyar nyelvű lektorált tanulmánykötet (Konstrukció és jelentés) 2011-re kész volt, 2012-ben jelent meg, tizenöt tanulmánnyal. • Beyond Dichotomies címmel kétnapos nemzetközi konferencia rendezése 2010-ben. • Rendszeres konferenciarészvétel, egyéni publikációk, PhD- (3), habilitációs (2) és nagydoktori (1) disszertációk. • Egy korpusz alapú funkcionális magyar nyelvtan fő fejezeteinek elkészítése (a Mondattan, Jelentéstan és Pragmatika részek fontos fejezetei). A kutatás a magyar nyelv leírásának új módszereit fejlesztette ki, továbbá a magyar nyelv egyes központi kategóriáit újraértelmezte, részletesebben kidolgozta, illetve korábban kevéssé vagy egyáltalán nem tárgyalt jelenségeinek egy sorát írta le, funkcionális kognitív keretben. Ezáltal a projekt új összetevővel gyarapította a magyar nyelvtudomány kutatási területét, jelentős új eredményeket mutatott fel, amelyek most kezdenek a nemzetközi szakirodalomban megjelenni (konferenciákon, majd publikációkban), új külföldi kutatási kapcsolatokat létesített, emelte a hazai nyelvtudomány színvonalát, és részt vett a kutatói utánpótlás nevelésében. | The main goal of the project as a basic research was to elaborate the theoretical and methodological base for the functional cognitive description of the Hungarian language, in harmony with the current international literature. This goal has been achieved. The concrete results of the project: • The double thematic issue of Acta Linguistica Hungarica (issues 2009/4, 2010/1, containing eleven papers). • The peer-reviewed volume of papers “Konstrukció és jelentés” (Construction and meaning), completed in 2011, containing fifteen papers. • The organization of the two-day international conference “Beyond Dichotomies”, October 2010. • Regular conference participation, individual papers, 3 PhD dissertations, 2 habilitaion dissertations, 1 DSc dissertation. • The main chapters of Syntax, Semantics and Pragmatics in a corpus based functional Hungarian grammar. The research project has developed new methods in the description of the Hungarian language, re-interpreted or elaborated in detail certain central categories of the Hungarian language, described linguistic phenomena less treated or not studied earlier, in the functional cognitive framework. The project added a new component to the research domains of Hungarian linguistics, presented significant new results, in the process of being published in the international discourse, established new research contacts, increased the level of Hungarian linguistics, and took part in the training of young researchers

A protein assembly mediates Xist localization and gene silencing

Nuclear compartments have diverse roles in regulating gene expression, yet the molecular forces and components that drive compartment formation remain largely unclear. The long non-coding RNA Xist establishes an intra-chromosomal compartment by localizing at a high concentration in a territory spatially close to its transcription locus and binding diverse proteins to achieve X-chromosome inactivation (XCI). The XCI process therefore serves as a paradigm for understanding how RNA-mediated recruitment of various proteins induces a functional compartment. The properties of the inactive X (Xi)-compartment are known to change over time, because after initial Xist spreading and transcriptional shutoff a state is reached in which gene silencing remains stable even if Xist is turned off. Here we show that the Xist RNA-binding proteins PTBP1, MATR3, TDP-43 and CELF1 assemble on the multivalent E-repeat element of Xist and, via self-aggregation and heterotypic protein–protein interactions, form a condensate in the Xi. This condensate is required for gene silencing and for the anchoring of Xist to the Xi territory, and can be sustained in the absence of Xist. Notably, these E-repeat-binding proteins become essential coincident with transition to the Xist-independent XCI phase, indicating that the condensate seeded by the E-repeat underlies the developmental switch from Xist-dependence to Xist-independence. Taken together, our data show that Xist forms the Xi compartment by seeding a heteromeric condensate that consists of ubiquitous RNA-binding proteins, revealing an unanticipated mechanism for heritable gene silencing

Integrated evolutionary analysis reveals antimicrobial peptides with limited resistance

Antimicrobial peptides (AMPs) are promising antimicrobials, however, the potential of bacterial resistance is a major concern. Here we systematically study the evolution of resistance to 14 chemically diverse AMPs and 12 antibiotics in Escherichia coli. Our work indicates that evolution of resistance against certain AMPs, such as tachyplesin II and cecropin P1, is limited. Resistance level provided by point mutations and gene amplification is very low and antibiotic-resistant bacteria display no cross-resistance to these AMPs. Moreover, genomic fragments derived from a wide range of soil bacteria confer no detectable resistance against these AMPs when introduced into native host bacteria on plasmids. We have found that simple physicochemical features dictate bacterial propensity to evolve resistance against AMPs. Our work could serve as a promising source for the development of new AMP-based therapeutics less prone to resistance, a feature necessary to avoid any possible interference with our innate immune system

Pcl-PRC2 is needed to generate high levels of H3-K27 trimethylation at Polycomb target genes

PRC2 is thought to be the histone methyltransferase (HMTase) responsible for H3-K27 trimethylation at Polycomb target genes. Here we report the biochemical purification and characterization of a distinct form of Drosophila PRC2 that contains the Polycomb group protein polycomblike (Pcl). Like PRC2, Pcl-PRC2 is an H3-K27-specific HMTase that mono-, di- and trimethylates H3-K27 in nucleosomes in vitro. Analysis of Drosophila mutants that lack Pcl unexpectedly reveals that Pcl-PRC2 is required to generate high levels of H3-K27 trimethylation at Polycomb target genes but is dispensable for the genome-wide H3-K27 mono- and dimethylation that is generated by PRC2. In Pcl mutants, Polycomb target genes become derepressed even though H3-K27 trimethylation at these genes is only reduced and not abolished, and even though targeting of the Polycomb protein complexes PhoRC and PRC1 to Polycomb response elements is not affected. Pcl-PRC2 is thus the HMTase that generates the high levels of H3-K27 trimethylation in Polycomb target genes that are needed to maintain a Polycomb-repressed chromatin state