574 research outputs found
Neural precursor cells rescue symptoms of Rett syndrome by activation of the Interferon γ pathway.
No full textThe beneficial effects of Neural Precursor Cell (NPC) transplantation in several neurological disorders are well established and they are generally mediated by the secretion of immunomodulatory and neurotrophic molecules. We therefore investigated whether Rett syndrome (RTT), that represents the first cause of severe intellectual disability in girls, might benefit from NPC-based therapy. Using in vitro co-cultures, we demonstrate that, by sensing the pathological context, NPC-secreted factors induce the recovery of morphological and synaptic defects typical of Mecp2 deficient neurons. In vivo, we prove that intracerebral transplantation of NPCs in RTT mice significantly ameliorates neurological functions. To uncover the molecular mechanisms underpinning the mediated benefic effects, we analyzed the transcriptional profile of the cerebellum of transplanted animals, disclosing the possible involvement of the Interferon γ (IFNγ) pathway. Accordingly, we report the capacity of IFNγ to rescue synaptic defects, as well as motor and cognitive alterations in Mecp2 deficient models, thereby suggesting this molecular pathway as a potential therapeutic target for RTT. [Abstract copyright: © 2024. The Author(s).
Neural Precursor Cells as a potential therapeutic approach for Rett Syndrome: identification of the involved molecular mechanisms
No full textRett syndrome (RTT) is a rare neurodevelopmental disorder, mostly caused by sporadic mutations in the X linked MECP2 gene. RTT, the primary cause of severe intellectual disability in females, currently lacks a cure; nonetheless, the FDA recently approved the first therapy utilizing a tripeptide of IGF1.
Neural Precursor Cells (NPCs) can sense the pathological environment when transplanted in it, they secrete beneficial factors that promote immunomodulation, neuroprotection, brain plasticity. These healing functions render NPCs an interesting cellular therapy for treating several neurodegenerative disorders. Since no study addressed their efficacy in neurodevelopmental diseases, we investigated their therapeutic potential in RTT, demonstrating their efficacy in vitro and in vivo. In vivo, we proved significant amelioration of the cognitive and motor defects of RTT mice, together with an increased lifespan, after NPCs transplantation. Through a transwell-based co-culture system, we observed that NPCs promote morphological and synaptic rescues in Mecp2 null neurons, demonstrating that NPCs-mediated beneficial effects arise through “bystander” and paracrine mechanisms.
RNA-seq studies of transplanted mice identified a candidate molecule involved in the benefic effects. Likely, the observed beneficial effects depend on the activation of different pathways. Therefore, my PhD studies are focused on exploiting a transwell-based co-culture system to identify the molecular mechanisms set in motion by NPCs in Mecp2-KO neurons.
Through a Bulk RNA-seq performed on immature neurons maintained, or not, in co-culture with NPCs we demonstrated positive effects on KO neurons when exposed to the NPCs secreted factors (e.g., enhancement in the synaptic compartment, typically defective in Rett neurons). Simultaneously, to understand which molecules are secreted by NPCs when exposed to the Mecp2-KO environment, their transcriptional profile is being investigated.
All data will be presented in the poster session to illustrate the value of this cellular approach in treating RTT and/or in identifying new defective pathways with putative therapeutic value
Un libro de horas iluminado para Alfonso de Borja : influencia de los grabados alemanes en la miniaturade la Corona de Aragon a mediados del siglo 14. / Francesca Manzari.
No full textIl saggio ricostruisce il contesto di produzione di un raro esempio di libro d’ore valenziano della metà del Quattrocento, indagando a fondo i diversi aspetti del raffinato manufatto. Il repertorio decorativo secondario viene ricondotto alla produzione valenziana, mentre le carte incipitarie maggiori, dotate di straordinarie ma inusuali bordure miniate, vengono spiegate identificandone i modelli nella carte da gioco prodotte da un proto-incisore tedesco, spesso utilizzato come repertorio di modelli anche in ambito fiammingo. L’identificazione di un ritratto del destinatario e del suo nome, Alfonso, insieme all’indagine “archeologica” sulle tracce di fogli perduti hanno permesso di proporre Alfonso Borgia, quale committente, alla metà del secolo, prima della sua elezione come papa Callisto IIIThe essay reconstructs the context of production of a rare example of Valencian Book of Hours from the mid-15th century, investigating in-depth the different features of the elegant artefact. The secondary decorative repertory is linked with the illuminated production at Valencia, while the major incipit pages, with extraordinary but unusual illuminated borders, are explained identifying their models in the printed playing cards produced by a German engraver; these were used as model books especially in Flanders. The identification of the owner’s portrait and name, Alfonso, together with the “archeological” analysis of the traces of lost leaves, have enabled the author to propose Alfonso Borgia as the patron, dating the book to the middle of the century, before his election as pope Callixtus II
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Francesca Bertini
No full textFrancesca Bertini was an extremely careful guardian of her image and legacy throughout her whole life. A major star of the international silent screen, she has recounted her hugely successful career in different autobiographic writings and interventions. An invaluable source of information for the history of Italian cinema, these documents are notoriously reticent—and sometimes unreliable—about certain personal details of her life. For example, she never revealed to have been first registered in 1892 at an orphanage in Florence as Elena Taddei, the daughter of Adelina di Venanzio Fratiglioni, a single mother and possibly a stage actress (Jandelli 2006, 31-2). While many sources indicate her first surname to be Seracini, the only concrete information we have about her acquired identity is that she became Elena Vitiello in 1910, when her mother married Arturo Vitiello, a Neapolitan propman or furniture dealer. Bertini was introduced to the sprightly Neapolitan theatrical milieu at an early age. She got her first, supporting role on stage when she was just seventeen, in the widely acclaimed 1909 production of “Assunta Spina”—an intense southern melodrama by reputed author Salvatore Di Giacomo. One of the most representative texts of the new Neapolitan popular theater, “Assunta Spina” was later transposed on screen by Bertini in 1915. The final result is still regarded as one of the masterpieces of Italian silent cinema and an emblematic example of Verist cinema. By 1915, Bertini had already been cast in more than 50 films, including many one and two-reel historical reconstructions and a few features. The following years saw her continuing to grow in popularity, with her films gaining huge acclaim wherever they were presented, from Europe to Latin America and from Russia to the United States
Identification of novel molecules by which Mecp2 knock-out astrocytes exert a synaptotoxic action on neurons
No full textBackground. Over 95% of Rett syndrome (RTT) cases are given by mutations in the X-linked methyl-CpG-binding protein 2 (MECP2) gene. Although initial studies supported a role for MeCP2 exclusively in neurons, several recent data indicate the involvement also of astrocytes, which can affect neuronal maturation through non-cell autonomous mechanisms. Nevertheless, many aspects of astrocyte dysfunctions in RTT remain still unknown.
Objectives: According to the crucial role of astrocytes in promoting synapse formation and functioning, and the profound synaptic alterations in RTT, we investigated the influence of Mecp2 null astrocytes on synaptic maturation and we explored the involvement of two molecules in the occurrence of synaptic defects.
Methods: To reproduce in vitro the heterozygous condition of RTT brains, we tested the effect of null astrocytes or their conditioned medium (ACM) on WT neurons. By immunufluorescence we analysed pre- and post-synaptic densities in cultured neurons. RNA sequencing was used to gain insight into the involved molecular mechanisms.
Results: We demonstrated that Mecp2 null astrocytes dramatically affect synaptogenesis and synaptic functionality, and molecular analyses highlighted in null astrocytes both the activation of an inflammatory pathway and a concomitant reduction in cholesterol metabolism. As validation of these underscored molecular mechanisms, we proved that Mecp2 null astrocytes, when in culture with WT neurons, express and secrete excessive levels of Interleukin-6 (IL-6), which exerts a synaptotoxic action. Indeed, we found that the recombinant IL-6 causes synaptic defects in WT neurons and, coherently, a neutralizing IL-6 antibody rescues KO astrocyte-mediated synaptic alterations. In parallel, we observed a reduced cholesterol metabolism in Mecp2 null astrocytes and demonstrated that cholesterol supplementation reverts synaptic defects.
Conclusion: These in vitro data constitute the rationale for studying the pathogenic role of IL-6 and cholesterol in Mecp2 deficient mice and explore novel therapeutic strategies targeting these two factors to improve RTT symptoms
Le funzioni delle citazioni bibliche nella letteratura della Slavia ortodossa
No full textBiblical quotations play a central role in the literature of Slavia orthodoxa. Their
importance, together with the necessity of their systematic study, has been underlined
several times. The biblical element should be analysed at several levels, within differ
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ent literary forms. First it should be identified and classified, then understood in the
context of liturgy and liturgical books. Through biblical quotations, the author gave an
interpretation of history and present situation according to the Holy Scripture and, by
means of rhetoric, he tried to make the biblical message actual and to renew its meta
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morphic power. The present study focuses on the function biblical quotations have in
some of the most representative literary forms of Slavia orthodoxa. M. Garzaniti analy
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ses hagiographic texts, pilgrimage tales and chronicles; F. Romoli sermons and spiritual
teachings
Author Correction: Biodiversity estimates and ecological interpretations of meiofaunal communities are biased by the taxonomic approach (Communications Biology, (2018), 1, 1, (112), 10.1038/s42003-018-0119-2)
No full textIn the original published version of the article, the acknowledgements incorrectly omitted a statement acknowledging the availability of public data through the authors’ funding from the Gulf of Mexico Research Initiative. This information was also missing from the Data Availability statement. In addition, the original version of the acknowledgements did not accurately reflect the relative funding to author Francesca Leasi from multiple sources. These errors have been corrected in the HTML and PDF versions of the article
DIFFERENTIAL FORMS IN CARNOT GROUPS AFTER M. RUMIN: AN INTRODUCTION
No full textThese notes are taken from the Master Thesis of the second author
(written under the supervision of B. Franchi and P. Pansu) and are partially
based on a PhD course given by the first author at the University of Bologna
in 2012-2013. They are aimed to provide an elementary and comprehensive
introduction to the theory of differential forms in Carnot groups and to the
so-called Rumin’s complex
A morphological layer for the German part of the SMULTRON corpus
No full textA morphological layer for the German part of the SMULTRON corpus. Layer was annotated according to the STTS tagset and the annotation guidelines of the Tiger corpus.
Coordinator: Thomas Müller
Annotators: Francesca Caratti, Arne Recknagel
This distribution contains a morphological layer for the SMULTRON corpus [0].
The annotation process is described in :
@InProceedings{mueller2015,
author = {M\"uller, Thomas and Sch\"utze, Hinrich},
title = {Robust Morphological Tagging with Word Representations},
booktitle = {Proceedings of NAACL},
year = {2015},
}
[0] http://www.cl.uzh.ch/research/parallelcorpora/paralleltreebanks/smultron_en.htm
An American at the origins of European Sprachwissenshaft and Italian historiographical thought. William Dwight Whitney and his approach to linguistic issues
No full textThis contribution is dedicated to William Dwight Whitney (1827–1897), a scholar who generally has a modest space dedicated to him in the historiography of linguistics, despite his name and works having had considerable circulation among his contemporaries. His originality and method are outlined with particular attention being given to his reception in Europe and in the setting of Italian studies of theoretical and empirical linguistics.
Whitney was among the first to contest Schleicher's concept of language as a natural fact, claiming, instead, that it has social nature, as an ‘institution’ created by man; he was a forerunner in recognizing the relevance of signs and their value, and of language acquisition. In his demonstrations and in his methods he proposes a science of historical linguistics but at the same time it is open to 20th century linguistics and the concept of language as a complex system ordered and crossed by relationships. Both his unique approach to the study of Sanskrit, which emphasised the study of its use and its variants, and his interest for modern languages, makes him a particularly interesting scholar, as he and his reception testify the rise, in Europe and especially in Italy, of a new approach to linguistic issues, no longer exclusively historical-comparative, but also theoretical and general.
Nonetheless, Whitney ought to occupy a prominent place in the history of linguistics, because he was also the author of one of the first introductory texts of the discipline, which was published in 1875; in that same year a French translation came out, which was soon followed by an Italian, and a German translation (both 1876).The number of almost contemporaneous translations gives an idea of the gap which a general and introductory work like Whitney's filled and illustrates that there was a clear need for it.
In several works, including recent ones, De Mauro identified the specific characteristics of Italian linguistic studies: we can find a good many of these traits in Whitney as well. Although the fruitful contribution of Whitney's ideas in an environment which is ‘naturally’ inclined towards the themes and methods the American linguist dealt with, i.e., the ‘Italian linguistic school’, has not been fully recognised until now, it is undeniable that his ideas provided an important stimulus for new interpretations and new models
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