1,592 research outputs found
"La materia quando inizia a soffrire": Denial Figures in Guido Morselli's Work
No full textopenIl presente lavoro si propone di indagare la questione della crisi del soggetto così come discussa dall'autore italiano Guido Morselli, nelle diverse sedi dei romanzi, della produzione saggistica e del diario personale. Da qui si analizzeranno temi quali il solipsismo e gli interrogativi esistenziali, fin dai loro primi riverberi nella filosofia centro-europea di fine Ottocento, inizio Novecento.The present work aims yo investigate the issue of the crisis of the subject, as it is discussed by the Italian author Guido Morselli, on his novels, essays and personal diary. We will also analyze topics such as solipsism and existential questions from their first reverberations on the late eighteen century and early nineteen century middle European philosophy
C-terminal fluorescent labeling impairs functionality of DNA mismatch repair proteins
No full textThe human DNA mismatch repair (MMR) process is crucial to maintain the integrity of the genome and requires many different proteins which interact perfectly and coordinated. Germline mutations in MMR genes are responsible for the development of the hereditary form of colorectal cancer called Lynch syndrome. Various mutations mainly in two MMR proteins, MLH1 and MSH2, have been identified so far, whereas 55% are detected within MLH1, the essential component of the heterodimer MutLα (MLH1 and PMS2). Most of those MLH1 variants are pathogenic but the relevance of missense mutations often remains unclear. Many different recombinant systems are applied to filter out disease-associated proteins whereby fluorescent tagged proteins are frequently used. However, dye labeling might have deleterious effects on MutLα's functionality. Therefore, we analyzed the consequences of N- and C-terminal fluorescent labeling on expression level, cellular localization and MMR activity of MutLα. Besides significant influence of GFP- or Red-fusion on protein expression we detected incorrect shuttling of single expressed C-terminal GFP-tagged PMS2 into the nucleus and found that C-terminal dye labeling impaired MMR function of MutLα. In contrast, N-terminal tagged MutLαs retained correct functionality and can be recommended both for the analysis of cellular localization and MMR efficiency
N‐terminus of hMLH1 confers interaction of hMutLα and hMutLβ with hMutSα
No full textMismatch repair is a highly conserved system that ensures replication fidelity by repairing mispairs after DNA synthesis. In humans, the two protein heterodimers hMutSα (hMSH2‐hMSH6) and hMutLα (hMLH1‐hPMS2) constitute the centre of the repair reaction. After recognising a DNA replication error, hMutSα recruits hMutLα, which then is thought to transduce the repair signal to the excision machinery. We have expressed an ATPase mutant of hMutLα as well as its individual subunits hMLH1 and hPMS2 and fragments of hMLH1, followed by examination of their interaction properties with hMutSα using a novel interaction assay. We show that, although the interaction requires ATP, hMutLα does not need to hydrolyse this nucleotide to join hMutSα on DNA, suggesting that ATP hydrolysis by hMutLα happens downstream of complex formation. The analysis of the individual subunits of hMutLα demonstrated that the hMutSα–hMutLα interaction is predominantly conferred by hMLH1. Further experiments revealed that only the N‐terminus of hMLH1 confers this interaction. In contrast, only the C‐terminus stabilised and co‐immunoprecipitated hPMS2 when both proteins were co‐expressed in 293T cells, indicating that dimerisation and stabilisation are mediated by the C‐terminal part of hMLH1. We also examined another human homologue of bacterial MutL, hMutLβ (hMLH1–hPMS1). We show that hMutLβ interacts as efficiently with hMutSα as hMutLα, and that it predominantly binds to hMutSα via hMLH1 as well
Phosphorylation-dependent signaling controls degradation of DNA mismatch repair protein PMS2
No full textMutLα, a heterodimer consisting of MLH1 and PMS2, plays an important role in DNA mismatch repair and has been shown to be additionally involved in several other important cellular mechanisms. Previous work indicated that AKT could modulate PMS2 stability by phosphorylation. Still, the mechanisms of regulation of MutLα remain unclear. The stability of MutLα subunits was investigated by transiently overexpression of wild type and mutant forms of MLH1 and PMS2 using immunoblotting for measuring the protein levels after treatment. We found that treatment with the cell-permeable serine/threonine phosphatase inhibitor, Calyculin, leads to degradation of PMS2 when MLH1 or its C-terminal domain is missing or if amino acids of MLH1 essential for PMS2 interaction are mutated. In addition, we discovered that the C-terminal tail of PMS2 is relevant for this Calyculin-dependent degradation. A direct involvement of AKT, which was previously described to be responsible for PMS2 degradation, could not be detected. The multi-kinase inhibitor Sorafenib, in contrast, was able to avoid the degradation of PMS2 which postulates that cellular phosphorylation is involved in this process. Together, we show that pharmacologically induced phosphorylation by Calyculin can induce the selective proteasome-dependent degradation of PMS2 but not of MLH1 and that the PMS2 degradation could be blocked by Sorafenib treatment. Curiously, the C-terminal Lynch Syndrome-variants MLH1L749P and MLH1Y750X make PMS2 prone to Calyculin induced degradation. Therefore, we conclude that the specific degradation of PMS2 may represent a new mechanism to regulate MutLα.Fil: Hinrichsen, Inga. University Clinic Frankfurt; AlemaniaFil: Weßbecher, Isabel M.. University Clinic Frankfurt; AlemaniaFil: Huhn, Meik. University Clinic Frankfurt; AlemaniaFil: Passmann, Sandra. University Clinic Frankfurt; AlemaniaFil: Zeuzem, Stefan. University Clinic Frankfurt; AlemaniaFil: Plotz, Guido. University Clinic Frankfurt; AlemaniaFil: Biondi, Ricardo Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. University Clinic Frankfurt; AlemaniaFil: Brieger, Angela. University Clinic Frankfurt; Alemani
"Sailing around the World (1857-1859). Colonial Patterns, Native Societies, Global Resources in the Circumnavigation of the Austrian Frigate Novara"
No full textThis essay by Guido Abbattista analyzes the Austrian frigate Novara’s circumnavigation (1857–1859) as a paradigmatic case of nineteenth-century global exploration, set within the broader context of European imperial expansion and scientific ambition. Abbattista demonstrates how the Novara expedition, Austria’s first global voyage, was not only a naval and scientific enterprise but also a vehicle for projecting imperial prestige, asserting national identity, and gathering knowledge about colonial patterns, native societies, and global resources. Drawing on official reports, scientific publications, and ethnographic collections, the essay situates the Novara alongside other Austrian and European voyages, highlighting its role in consolidating Austria’s place on the world stage. The author explores the ideological underpinnings of the mission, especially as articulated by Karl von Scherzer, who framed the journey in terms of Eurocentric progress, racial hierarchies, and the civilizing mission of Europe—particularly the “Anglo-Saxon” model. The essay critically examines how the Novara’s documentation and collections contributed to museums and scientific institutions, while also reflecting the contradictions and exclusions of imperialist worldviews. Ultimately, Abbattista argues that the Novara expedition exemplifies the entanglement of science, empire, and global modernity, offering insight into the construction of “global Europeanness” and the enduring legacies of colonial encounters
Erratum to: Association Study between Coronary Artery Disease and rs1333049 Polymorphism at 9p21.3 Locus in Italian Population (Journal of Cardiovascular Translational Research, (2017), 10, 5-6, (455-458), 10.1007/s12265-017-9758-9)
No full textThe author affiliation for both Guido Iaccarino and Michele Ciccarelli is Medicine, Surgery and Dentistry, Scuola Medica Salernitana, University of Salerno. The currently mentioned affiliations (Department of Advanced Biomedical SciencesFederico II University NaplesItaly and IRCCS SDN Istituto di Ricerca Diagnostica e Nucleare Naples Italy respectively) are not correct
Missa luba : new edition and conductor's analysis
No full text"Since 1964 and the first printed edition of Missa Luba by Guido Haazen, this work has been performed countless numbers of times all over the world. Missa Luba continues to have a large number of performances each year, despite the fact that there is very little research available, and the only published edition is wholly insufficient in producing an authentic performance. To date, the following has not been published in any known academic publications: 1) a biography of Guido Haazen, 2) research into the first choir to sing Missa Luba, 3) a detailed explanation of the collective improvisational nature of the work, and 4) a comparison of the folk melodies used as models to the corresponding sections of each Mass movement. The purpose of this document is to provide a new edition of Missa Luba and an analysis of the work useful to a conductor. The reasons why a new edition is needed and what changes are made to the existing edition will be discussed, along with an analysis, which will cover the work's historical background, structure, and performance practice concerns. The document will incorporate recent research into this subject, especially that of interviews with Guido Haazen prior to his death in 2004, and a more accurate transcription of the original 1958 recording. Also, significant to this project is a description of the ethnic instruments used in the original performances of Missa Luba and suitable modern substitutions. Research conducted at the Central Africa Museum in Tervuren, Belgium will be primary in this discussion. The result of this document will be a new edition of Missa Luba, more accurately reflective of the 1958 recording and early performances, and will provide much needed research into its creation, structure, and performance. "--Abstract from author supplied metadata
Guido Fassò. Un itinerario filosofico tra diritto e natura umana
No full textWith this essay the author intends to examine the fundamental themes of the reflections of Guido Fassò, highlighting the relationship between juridical and moral experience, and following the genesis of this Bolognese philosopher's peculiar natural law approach which has both a sociological and realistic character
Diventare bolognese. L’ebreo converso Ippolito Boncompagni e i suoi legami con Guido Reni, Guido Signorini e Domenichino
No full textBecoming Bolognese: The Converted Jew Ippolito Boncompagni and his
Relationship
with Guido Reni, Guido Signorini and Domenichino
The essay moves from an introduction on Guido Reni’s friendship with the converted
Jew Ippolito Boncompagni, formerly Ruben Corcos, and presents the story
of the conversion of the four Corcos brothers (all of whom were baptized as
Catholics
in 1592 and took the name Boncompagni) as the backdrop to a discussion
of the Boncompagni collection of paintings inventoried in 1657. This
collection featured a remarkable number of Bolognese and Emilian works by
painters such as Reni, Guercino, Domenichino, Lanfranco, Albani, Sementi.
Through an analysis of the documents, it is established that a substantial number
of the works were owned by Ippolito, and the identification of some of them is
attempted. The study then focuses on Reni’s cousin and heir, the painter Guido
Signorini, bringing to light hitherto unpublished documents and new information
on the friendship between Signorini and Ippolito, and providing a close
reading of archival material concerning Reni’s will, inventory and Signorini’s
inheritance. The final section focuses on Ippolito and Domenichino. Archival
documents show that Ippolito
was financially involved not only with Guido
Reni, but also with Domenichino,
possibly as early as 1621–1623, and – after the
painter’s death in 1641 – with his widow. The Boncompagni owned two paintings
by Domenichino, one of which is an unknown Rebuke of Adam and Eve.
Expanding
on Richard Spear’s insights into the unusual iconography of another
version of the Rebuke by Domenichino
now in the Museum of Grenoble, the
author hypothesizes that these anomalies could reflect the Corcos’ Jewish background.
Finally, the study presents an interpretation of Boncompagni artistic
patronage
and collecting as instruments of self-representation, as well as means
to gain and consolidate social acceptanc
- …
